Drug Design

Structure- and Ligand-Based Approaches

Drug Design

Structure-based (SBDD) and ligand-based (LBDD) drug design are extremely important and active areas of research in both the academic and commercial realms. This book provides a complete snapshot of the field of computer-aided drug design and associated experimental approaches. Topics covered include X-ray crystallography, NMR, fragment-based drug design, free energy methods, docking and scoring, linear-scaling quantum calculations, QSAR, pharmacophore methods, computational ADME-Tox, and drug discovery case studies. A variety of authors from academic and commercial institutions all over the world have contributed to this book, which is illustrated with more than 200 images. This is the only book to cover the subject of structure and ligand-based drug design, and it provides the most up-to-date information on a wide range of topics for the practicing computational chemist, medicinal chemist, or structural biologist.

catalyst/confirm. San Diego, CA Accelrys.
catalyst/hyporefine. San Diego, CA: Accelrys.
phase 3.0. New York: Schrödinger, LLC; 2008.
http://www.bioinform.com/issues/12_41/features/150096-1.html.
http://www.eyesopen.com/products/applications/omega.html.
http://www.eyesopen.com/products/applications/rocs.html.
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed.
Abad-Zapatero, C. ; Metz, J. T. Ligand efficiency indices as guideposts for drug discovery. Drug Discov. Today 2005, 10, 464–469.
Abagyan, R. ; Totrov, M. High-throughput docking for lead generation. Curr. Opin. Chem. Biol. 2001, 5(4), 375–382.
Abagyan, R. ; Totrov, M. High-throughput docking for lead generation. Curr. Opin. Chem. Biol. 2001, 5, 375–382.
Abraham, M. H. ; Ibrahim, A. ; Zhao, Y. ; Acree, W. E. A data base for partition of volatile organic compounds and drugs from blood/plasma/serum to brain, and an LFER analysis of the data. J. Pharm. Sci. 2006, 95, 2091.
Abraham, M. H. The factors that influence permeation across the blood-brain barrier. Eur. J. Med. Chem. 2004, 39, 235.
Acronym for 2′-Deoxy-2′-Amino-Tetritol-N-(9-Methylene)-ImmH but the IUPAC name is 9-deaza-9-[[(2R,3S)-1,3,4-trihydroxybutan-2-ylamino]methyl]hypoxanthine. This acronym first appeared in Taylor et al., but as an oversight, was never defined; DATMe-ImmH is compound 19 in that manuscript.
Adams, C. ; Brantner, V. Estimating the cost of new drug development: is it really 802 million dollars? Health Affairs 2006, 25, 420.
Afantitis, A. ; Melagraki, G. ; Sarimveis, H. ; Koutentis, P. A. ; Markopoulos, J. ; Igglessi-Markopoulou, O. A novel QSAR model for predicting induction of apoptosis by 4-aryl-4H-chromenes. Bioorg. Med. Chem. 2006, 14, 6686–6694.
Agarwal, P. ; Billeter, S. ; Rajagopalan, P. ; Benkovic, S. ; Hammes-Schiffer, S. Network of coupled promoting motions in enzyme catalysis. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 2794–2799.
Agarwal, R. ; Spector, T. ; Parks, R. J. Tight-binding inhibitors. IV. Inhibition of adenosine deaminases by various inhibitors. Biochem. Pharmacol. 1977, 26, 359–367.
Agarwal, S. M. ; Jain, R. ; Bhattacharya, A. ; Azam, A. Inhibitors of Escherichia coli serine acetyltransferase block proliferation of Entamoeba histolytica trophozoites. Int. J. Parasitol. 2008, 38, 137–141.
Ahlstroem, M. A. ; Ridderstrom, M. ; Zamora, I. ; Luthman, K. CYP2C9 structure-metabolism relationships: optimizing the metabolic stability of COX-2 inhibitors. J. Med. Chem. 2007, 50, 4444.
Ahlstroem, M. A. ; Ridderstrom, M. ; Zamora, I. CYP2C9 structure-metabolism relationships: substrates, inhibitors, and metabolites. J. Med. Chem. 2007, 50, 5382.
Aires-de-Sousa, J. ; Gasteiger, J. Prediction of enantiomeric excess in a combinatorial library of catalytic enantioselective reactions. J. Comb. Chem. 2005, 7, 298–301.
Ajay, A. ; Walters, W. P. ; Murcko, M. A. Can we learn to distinguish between “drug-like” and “nondrug-like” molecules? J. Med. Chem. 1998, 41, 3314–3324.
Albert, J. S. ; et al. An integrated approach to fragment-based lead generation: philosophy, strategy and case studies from AstraZeneca's drug discovery programmes. Curr. Top. Med. Chem. 2007, 7, 1600–1629.
Allen, F. H. An experimental approach to mapping the binding surfaces of crystalline proteins. Acta Crystallogr. D Biol. Crystallogr. 2002, 58, 380–388.
Allen, K. N. ; Bellamacina, C. ; Ding, C. ; Jeffrey, C. ; Mattos, C. ; Petsko, G. A. ; Ringe, D. The Cambridge Structural Database: a quarter of a million crystal structures and rising. J. Phys. Chem. 1996, 100, 2605–2611.
Allen, K. N. ; Bellamacina, C. R. ; Ding, X. ; Jeffery, C. J. ; Mattos, C. ; Petsko, G. A. ; Ringe D. An experimental approach to mapping the binding surfaces of crystalline protein. J. Phys. Chem. 1996, 100, 2605–2611.
Allen, M. P. ; Tildesley, D. J. Computer Simulation of Liquids. New York: Oxford University Press; 1987.
Alorta, I. ; Loew, G. H. A 3D model of the ö opioid receptor and ligand-receptor complexes. Protein Eng. 1996, 9, 573.
Alter, M. J. Epidemiology of hepatitis C. Hepatology 1997, 26, 62S–65S.
Alvarez, J. C. High-throughput docking as a source of novel drug leads. Curr. Opin. Chem. Biol. 2004, 8, 365–370.
Amyes, T. L. ; Wood, B. M. ; Chan, K. ; Gerlt, J. A. ; Richard, J. P. Formation and stability of a vinyl carbanion at the active site of orotidine 5′-monophosphate decarboxylase: pKa of the C-6 proton of enzyme-bound UMP. J. Am. Chem. Soc. 2008, 130, 1574–1575.
Anderson, V. Ground state destabilization. In: Encyclopedia of Life Sciences. Chichester: John Wiley & Sons, Ltd.; 2001, 1–5.
Anisimov, V. ; Paneth, P. ISOEFF98: a program for studies of isotope effects using hessian modifications. J. Math. Chem. 1999, 26, 75–86.
Antoniou, D. ; Basner, J. ; Núñez, S. ; Schwartz, S. Computational and theoretical methods to explore the relation between enzyme dynamics and catalysis. Chem. Rev. 2006, 106, 3170–3187.
Appell, K. ; Baldwin, J. J. ; Egan, W. J. Combinatorial chemistry and high-throughput screening in drug discovery and development. In: Handbook of Modern Pharmaceutical Analysis, Ahuja, S ; Scypinski, S. ; Eds. San Diego, Academic Press; 2001, 23.
Aptula, A. O. ; Roberts, D. W. ; Cronin, M. T. D. ; Schultz, T. W. Chemistry-toxicity relationships for the effects of di- and trihydroxybenzenes to Tetrahymena pyriformis . Chem. Res. Toxicol. 2005, 18, 844–854.
Aqvist, J. ; Marelius, J. The linear interaction energy method for predicting ligand binding free energies. Comb. Chem. High Throughput Screen. 2001, 4(8), 613–626.
Archer, E. ; Maigret, B. ; Escrieut, C. ; Pradayrol, L. ; Fourmy, D. Rhodopsin crystal: new template yielding realistic models of G-protein-coupled receptors? Trends Pharmacol. Sci. 2003, 24, 36.
Archontis, G. ; Simonson, T. ; Karplus, M. Binding free energies and free energy components from molecular dynamics and Poisson-Boltzmann calculations: Application to amino acid recognition by aspartyl-tRNA. J. Mol. Biol. 2001, 306, 307–327.
Ash, S. ; Cline, M. A. ; Homer, R. W. ; Hurst, T. ; Smith, G. B. SYBYL line notation (SLN): a versatile language for chemical structure representation. J. Chem. Inf. Comput. Sci. 1997, 37, 71–79.
Asikainen, A. ; Ruuskanen, J. ; Tuppurainen, K. Spectroscopic QSAR methods and self-organizing molecular field analysis for relating molecular structure and estrogenic activity. J. Chem. Inf. Comput. Sci. 2003, 43(6), 1974–1981.
Austin, C. P. ; Brady, L. S. ; Insel, T. R. ; Collins, F. S. NIH Molecular Libraries Initiative. Science 2004, 306, 1138–1139.
Axe, F. U. ; Bembenek, S. D. ; Szalma, S. Three-dimensional models of histamine H3 receptor antagonist complexes and their pharmacophore. J. Mol. Graph. Model. 2006, 24, 456.
Azim, M. K. ; Ahmed, W. ; Khan, I. A. ; Rao, N. A. ; Khan, K. M. Identification of acridinyl hydrazides as potent aspartic protease inhibitors. Bioorg. Med. Chem. Lett. 2008, 18, 3011–3015.
Böhm, H.-J. LUDI: rule-based automatic design of new substituents for enzyme inhibitor leads. J. Comput. Aided Mol. Des. 1992, 6, 593–606.
Babaoglu, K. ; Simeonov, A. ; Irwin, J. J. ; Nelson, M. E. ; Feng, B. ; Thomas, C. J. ; Cancian, L. ; Costi, M. P. ; Maltby, D. A. ; Jadhav, A. ; Inglese, J. ; Austin, C. P. ; Shoichet, B. K. Comprehensive mechanistic analysis of hits from high-throughput and docking screens against β-lactamase. J. Med. Chem. 2008, 51, 2502–2511.
Babaoglu, K. ; Simeonov, A. ; Irwin, J. J. ; Nelson, M. E. ; Feng, B. ; Thomas, C. J. ; Cancian, L. ; Costi, M. P. ; Maltby, D. A. ; Jadhav, A. ; Inglese, J. ; Austin, C. P. ; Shoichet, B. K. Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase. J. Med. Chem. 2008, 51, 2502–2511.
Bagdassarian, C. K. ; Schramm, V. L. ; Schwartz, S. D. Molecular electrostatic potential analysis for enzymatic substrates, competitive inhibitors, and transition-state inhibitors. J. Am. Chem. Soc. 1996, 118, 8825–8836.
Bai, J. P. F. ; Utis, A. ; Crippen, G. ; He, H. D. ; Fischer, V. ; Tullman, R. ; Yin, H. Q. ; Hsu, C. P. ; Jing, Hwang, K. K. Use of classification regression tree in predicting oral absorption in humans. J. Chem. Inf. Comp. Sci. 2004, 44, 2061.
Balakin, K. V. ; Ivanenkov, Y. A. ; Skorenko, A. V. ; Nikolsky, Y. V. ; Savchuk, N. P. ; Ivashchenko, A. A. In silico estimation of DMSO solubility of organic compounds for bioscreening. J. Biomolec. Screen. 2004, 9, 22.
Balakin, K. V. ; Savchuk, N. P. ; Tetko, I. V. In silico approaches to prediction of aqueous and DMSO solubility of drug-like compounds: trends, problems and solutions. Curr. Med. Chem. 2006, 13, 223.
Baldwin, J. M. The probable arrangement of the helices in G protein-coupled receptors. EMBO J. 1993, 12 1693.
Baldwin, R. L. In search of the energetic role of peptide hydrogen bonds. J. Biol. Chem. 2003, 278(20), 17581–17588.
Banba, S. ; Guo, Z. ; Brooks, C. L., III . Efficient sampling of ligand orientations and conformations in free energy calculations using the lambda-dynamics method. J. Phys. Chem. B, 2000, 104(29),6903–6910.
Banerjee, A. ; Yang, W. ; Karplus, M. ; Verdine, G. L. Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA. Nature 2005 434, 612–618.
Bantia, S. ; Miller, P. J. ; Parker, C. D. ; Ananth, S. L. ; Horn, L. L. ; Kilpatrick, J. M. ; Morris, P. E. ; Hutchison, T. L. ; Montgomery, J. A. ; Sandhu, J. S. Purine nucleoside phosphorylase inhibitor BCX-1777 (Immucillin-H) – a novel potent and orally active immunosuppressive agent. Int. Immunopharmacol. 2001, 1, 1199–1210.
Barillari, C. ; Taylor, J. ; Viner, R. ; Essex, J. W. Classification of water molecules in protein binding sites. J. Am. Chem. Soc. 2007, 129(9), 2577–2587.
Barnum, D. ; Greene, J. ; Smellie, A. ; Sprague, P. Identification of common functional configurations among molecules. J. Chem. Inf. Comput. Sci. 1996, 36, 563–571.
Barreiro, G. ; Guimarães, C. R. W. ; Tubert-Brohman, I. ; Lyons, T. M. ; Tirado-Rives, J. ; Jorgensen, W. L. Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring. J. Chem. Info. Model. 2007, 47, 2416–2428.
Barreiro, G. ; Guimaraes, C. R. W. ; Tubert-Brohman, I. ; Lyons, T. M. ; Tirado-Rives, J. ; Jorgensen, W. L. Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring. J. Chem. Inf. Model. 2007, 47, 2416–2428.
Barreiro, G. ; Kim, J. T. ; Guimarães, C. R. W. ; Bailey, C. M. ; Domaoal, R. A. ; Wang, L. ; Anderson, K. S. ; Jorgensen, W. L. From docking false-positive to active anti-HIV Agent. J. Med. Chem. 2007, 50, 5324–5329.
Barresinoussi, F. ; et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune-deficiency syndrome (AIDS). Science 1983, 220(4599), 868–871.
Barril, X. ; Brough, P. ; Drysdale, M. ; Hubbard, R. E. ; Massey, A. ; Surgenor, A. ; Wright, L. Structure-based discovery of a new class of Hsp90 inhibitors. Bioorg. Med. Chem. Lett. 2005, 15, 5187–5191.
Barsacchi, D. ; Cappiello, M. ; Tozzi, M. ; Del Corso, A. ; Peccatori, M. ; Camici, M. ; Ipata, P. ; Mura, U. Purine nucleoside phosphorylase from bovine lens: purification and properties. Biochim. Biophys. Acta 1992, 1160, 163–170.
Bartels, C. ; Karplus, M. Multidimensional adaptive umbrella sampling: applications to main chain and side chain peptide conformations. J. Comput. Chem. 1997, 18(12), 1450–1462.
Bartenschlager, R. ; Ahlborn-Laake, L. ; Mous, J. ; Jacobsen, H. Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions. J. Virol. 1993, 67, 3835–3844.
Bashford, D. ; Case , D. A. Generalized born models of macromolecular solvation effects. Annu. Rev. Phys. Chem. 2000, 51, 129–152.
Baurin, N. , et al. Design and characterization of libraries of molecular fragments for use in NMR screening against protein targets. J. Chem. Inf. Comput. Sci. 2004, 44, 2157–2166.
Baxter, E. W. ; Conway, K. A. ; Kennis, L. ; Bischoff, F. ; Mercken, M. H. ; De Winter, H. L. ; Reynolds, C. H. ; Tounge, B. A. ; Luo, C. ; Scott, M. K. ; Huang, Y. ; Braeken, M. ; Pieters, S. M. A. ; Berthelot, D. J. C. ; Masure, S. ; Bruinzeel, W. D. ; Jordan, A. D. ; Parker, M. H. ; Boyd, R. E. ; Qu, J. ; Alexander, R. S. ; Brenneman, D. E. ; Reitz, A. B. 2-amino-3,4-dihydroquinazolines as inhibitors of BACE-1 (β-site APP cleaving enzyme): use of structure based design to convert a micromolar hit into a nanomolar lead. J. Med. Chem. 2007, 50(18), 4261–4264.
Beck, M. E. Do Fukui function maxima relate to sites of metabolism? A critical case study. J. Chem. Inf. Model. 2005, 45, 273.
Becker, O. M. ; Marantz, Y. ; Shacham, S. ; Inbal, B. ; Heifetz, A. ; Kalid, O. ; Bar-Haim, S. ; Warshaviak, D. ; Fichman, M. ; Noiman, S. G Protein-coupled receptors: In silico drug discovery in 3D. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 11304.
Bemis, G. W. ; Murcko, M. A. The properties of known drugs. 1. Molecular frameworks. J. Med. Chem. 1996, 39, 2887–2893.
Bennett, C. H. Efficient estimation of free energy differences from Monte Carlo data. J. Comput. Phys. 1976, 22, 245–268.
Berman, H. M. ; Westbrook, J. ; Feng, Z. ; Gilliland, G. ; Bhat, T. N. ; Weissig, H. ; Shindyalov, I. N. ; Bourne, P. E. The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235–242.
Berman, H. M. ; Wetbrook, J. ; Feng, Z. ; Gilliland, G. ; Bhat, T. N. ; Weissig, H. ; Shindyalov, I. N. ; Bourne, P. E. The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235–242.
Bernstein, F. C. ; Koetzle, T. F. ; Williams, G. J. B. ; Meyer, E. F., Jr. ; Brice, M. D. ; Rogers, J. R. ; Kennard, O. ; Shimanouchi, T. ; Tasumi, M. The Protein Data Bank. A computer-based archival file for macromolecular structures. J. Mol. Biol. 1977, 112, 535–547.
Berti, P. ; McCann, J. Toward a detailed understanding of base excision repair enzymes: transition state and mechanistic analyses of N-glycoside hydrolysis and N-glycoside transfer. Chem. Rev. 2006, 106, 506–555.
Berti, P. J. ; Blanke, S. R. ; Schramm, V. L. Transition state structure for the hydrolysis of NAD+ catalyzed by diphtheria toxin. J. Am. Chem. Soc. 1997, 119, 12079–12088.
Berti, P. J. ; Tanaka, K. S. E . Transition state analysis using multiple kinetic isotope effects: mechanisms of enzymatic and non-enzymatic glycoside hydrolysis and transfer. Adv. Phys. Org. Chem. 2002, 37, 239–314.
Besalu, E. ; Girones, X. ; Amat, L. ; Carbo-Dorca, R. Molecular quantum similarity and the fundamentals of QSAR. Acc. Chem. Res. 2002, 35, 289–295.
Betzi, S. ; Restouin, A. ; Opi, S. ; Arold, S. T. ; Parrot, I. ; Guerlesquin, F. ; Morelli, X. ; Collette, Y. Protein-protein interaction inhibition (2P2I) combining high throughput and virtual screening: application to the HIV-1 nef protein. Proc. Natl. Acad. Sci. USA 2007, 104, 19256–19261.
Beusen, D. D. ; Marshall, G. R. Pharmacophore definition using the active analog approach. In: Pharmacophore Perception, Development, and Use in Drug Design, Güner, O. F. ; Ed. La Jolla, CA: International University Line; 2000, 23–45.
Beutler, T. C. ; Mark, A. E. ; van Schaik, R. C. ; Gerber, P. R. ; van Gunsteren, W. F. Avoiding singularities and numerical instabilities in free energy calculations based on molecular simulations. Chem. Phys. Lett. 1994, 222, 529–539.
Bhal, S. K. ; Kassam, K. ; Peirson, I. G. ; Pearl, G. M. The Rule of Five revisited: applying log D in place of log P in drug-likeness filters. Mol. Pharm. 2007, 4, 556.
Bianchet, M. ; Seiple, L. ; Jiang, Y. ; Ichikawa, Y. ; Amzel, L. ; Stivers, J. Electrostatic guidance of glycosyl cation migration along the reaction coordinate of uracil DNA glycosylase. Biochemistry 2003, 42, 12455–12460.
Bigeleisen, J. ; Wolsberg, M. Theoretical and experimental aspects of isotope effects in chemical kinetics. Adv. Chem. Phys. 1958, 1, 15–76.
Bigeleisen, J. The relative reaction velocities of isotopic molecules. J. Chem. Phys. 1949, 17, 675–678.
Biller, S. A. ; Custer, L. ; Dickinson, K. E. ; Durham, S. K. ; Gavai, A. V. ; Hamann, L. G. ; Josephs, J. L. ; Moulin, F. ; Pearl, G. M. ; Flint, O. P. ; Sanders, M. ; Tymiak, A. A. ; Vaz, R. The challenge of quality in candidate optimization. In: Biotechnology: Pharmaceutical Aspects, 1(Pharmaceutical Profiling in Drug Discovery for Lead Selection), Arlington, AAPS Press, 2004, 413.
BioCryst Pharmaceuticals Inc ., Forodesine, October 7, 2009, http://www.biocryst.com/forodesine.
Birck, M. ; Schramm, V. Binding causes the remote [5′-3H]thymidine kinetic isotope effect in human thymidine phosphorylase. J. Am. Chem. Soc. 2004, 126, 6882–6883.
Birck, M. ; Schramm, V. Nucleophilic participation in the transition state for human thymidine phosphorylase. J. Am. Chem. Soc. 2004, 126, 2447–2453.
Bissantz, C. ; Bernard, P. ; Hibert, M .; Rognan, D. Protein-Based Virtual Screening of Chemical Databases. II. Are Homology Models of G-Protein Coupled Receptors Suitable Targets? Proteins 2003, 50, 5.
Bitetti-Putzer, R. ; Yang, W. ; Karplus, M. Generalized ensembles serve to improve the convergence of free energy simulations. Chem. Phys. Lett. 2003, 377, 633–641.
Blagović, M. U. ; Tirado-Rives, J. ; Jorgensen, W. L. Structural and energetic analyses for the effects of the K103N mutation of HIV-1 reverse transcriptase on efavirenz analogs. J. Med. Chem. 2004, 46, 2389–2392.
Blair, W. S. ; et al. HIV-1 entry – an expanding portal for drug discovery. Drug Discov. Today 2000, 5(5), p. 183–194.
Blaney, J. ; Nienaber, V. ; Burley, S. Fragment-based lead discovery and optimisation using X-ray crystallography, computational chemistry, and high-throughput organic synthesis. In: Fragment-Based Approaches in Drug Discovery: Methods and Principles in Medicinal Chemistry, Vol. 34, Jahnke, W. ; Erlanson, D. ; Eds. Wennheim: Wiley–VCH; 2006, 215–248.
Blaney, J. ; Nienaber, V. ; Burley, S. K. In: Fragment-Based Approaches in Drug Discovery, Jahnke, W. ; and Erlanson, D. A. ; Eds. Weinheim: Wiley VCH; 2006, 215–248.
Bleicher, K. ; Lin, M. ; Shapiro, M. ; Wareing, J. Diffusion edited NMR: screening compound mixtures by affinity NMR to detect binding ligands to vancomycin. J. Org. Chem. 1998, 63, 8486–8490.
Bleicher, K. H. ; Green, L. G. ; Martin, R. E. ; Rogers-Evans, M. Ligand identification for G-protein-coupled receptors: a lead generation perspective. Curr. Opin. Chem. Biol. 2004, 8, 287.
Blondel, A. Ensemble variance in free energy calculations by thermodynamic integration: theory, optimal alchemical path, and practical solutions. J. Comput. Chem. 2004, 25(7), 985–993.
Blow, D. M. A rearrangement of Cruickshanks formulae for the diffraction-component precision index. Acta Crystallogr., Sect. D 2002, D58, 792–797.
Blow, D. Outline of Crystallography for Biologists. New York, NY: Oxford University Press; 2002.
Blundell, T. L. ; Jhoti, H. ; Abell, C. High-throughput crystallography for lead discovery in drug design. Nat. Rev. Drug Discov. 2002, 1(1), 45–54.
Bockaert, J. ; Pin, J. P. Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J. 1999, 18, 1723.
Boehm, H. J. ; et al. Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guided optimization. A promising alternative to random screening. J. Med. Chem. 2000, 43, 2664–2674.
Boehm, J. C. ; Adams, J. L. New inhibitors of p38 kinase. Expert Opin. Ther. Pat. 2000, 10, 25–37.
Boehm, J. C. ; Smietana, J. M. ; Sorenson, M. E. ; Garigipati, R. S. ; Gallagher, T. F. ; Sheldrake, P. L. ; Breadbeer, J. ; Badger, A. M. ; Laydon, J. T. ; Lee, J. C. ; Hillegass, L. M. ; Griswold, D. E. ; Breton, J. J. ; Chabot-Fletcher, M. C. ; Adams, J. L. 1-Substituted 4-aryl-5-pyridinylimidazoles: a new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency. J. Med. Chem. 1996, 39, 3929–3937.
Bogan, A. A. ; Thorn, K. S. Anatomy of hot spots in protein interfaces. J. Mol. Biol. 1998, 280, 1–9.
Bohacek, R. S. ; McMartin, C. ; Guida, W. C. The art and practice of structure-based drug design: a molecular modeling perspective. Med. Res. Rev. 1996, 16, 3–50.
Bohacek, R. S. ; McMartin, C. ; Guida, W. C. The art and practice of structure-based drug design: a molecular modelling perspective. Med. Res. Rev. 1996, 16, 3–50.
Bohacek, R. S. ; McMartin, C. Definition and display of steric, hydrophobic, and hydrogen-bonding properties of ligand binding sites in proteins using Lee and Richards accessible surface: validation of a high-resolution graphical tool for drug design. J. Med. Chem. 1992, 35, 1671–1684.
Bohm, H. J. The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure. J. Comput. Aid. Mol. Des. 1994, 8, 243–256.
Bolin, J. ; Filman, D. ; Matthews, D. ; Hamlin, R. ; Kraut, J. Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 Å resolution. I. General features and binding of methotrexate. J. Biol. Chem. 1982, 257, 13650–13662.
Boresch, S. ; Karplus, M. The Jacobian factor in free energy simulations. J. Chem. Phys. 1996, 105(12), 5145–5154.
Boresch, S. ; Tettinger, F. ; Leitgeb, M. ; Karplus, M. Absolute binding free energies: a quantitative approach for their calculation. J. Phys. Chem. A 2003, 107(35), 9535–9551.
Borodina, Y. ; Rudik, A. ; Filimonov, D. ; Kharchevnikova, N. ; Dmitriev, A. ; Blinova, V. ; Poroikov, V. A new statistical approach to predicting aromatic hydroxylation sites. Comparison with model-based approaches. J. Chem. Inf. Comp. Sci. 2004, 44, 1998.
Bowman, M. J. ; Byrne, S. ; Chmielewski, J. Switching between allosteric and dimerization inhibition of HIV-1 protease. Chem. Biol. 2005, 12(4), 439–444.
Boyd D. Successes of computer-assisted molecular design. In: Reviews in Computational Chemistry, Boyd, D. ; Lipkowitz, K. B. ; Eds. New York, NY: VCH; 1990, 355–371.
Boyer, S. ; Arnby, C. ; Hasselgren, C. ; Carlsson, L. ; Smith, J. ; Stein, V. ; Glen, R. C. Reaction site mapping of xenobiotic biotransformations. J. Chem. Inf. Model. 2007, 47, 583.
Brüstle, M. ; Beck, B. ; Schindler, T. ; King, W. ; Mitchell, T. ; Clark, T. Descriptors, physical properties, and drug-likeness. J. Med. Chem. 2002, 45, 3345–3355.
Brandsdal, B. O. ; Österberg, F. ; Almlöf, M. ; Feierberg, I. ; Luzhkov, V. B. ; Åqvist, J. Free energy calculations and ligand binding. Adv. Prot. Chem. 2003, 66, 123–158.
Braunheim, B. ; Miles, R. ; Schramm, V. ; Schwartz, S. Prediction of inhibitor binding free energies by quantum neural networks: nucleoside analogues binding to trypanosomal nucleoside hydrolase. Biochemistry 1999, 38, 16076–16083.
Breiman L. Random forests. J. Mach. Learn. Res. 2001, 45, 5–32.
Breiman, L. ; Friedman, J. H. ; Olshen, R. A. ; Stone, C. J. Classification and Regression Trees. Belmont, CA: Wadsworth International Group; 1984.
Breiman, L. ; Friedman, J. H. ; Olshen, R. A. ; Stone, C. J. Classification and Regression Trees. Florence, KY: Wadsworth; 1984.
Brenk, R. ; Irwin, J. J. ; Shoichet, B. K. Here be dragons: docking and screening in an uncharted region of chemical space. J. Biomol. Screen. 2005, 10, 667–674.
Bron, C. ; Kerbosch, J. Algorithm 457: finding all cliques of an undirected graph. Commun. ACM 1973, 16, 575–577.
Brooijmans, N. ; Kuntz, I. D. Molecular recognition and docking algorithms. Annu. Rev. Biophys. Biomol. Struct. 2003, 335–373.
Brooks, B. R. ; Bruccoleri, R. E. ; Olafson, B. D. ; States, D. J. ; Swaminathan, S. ; Karplus, M. CHARMM: a program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 1983, 4(2), 187–217.
Brooks, B. R. ; Bruccoleri, R. E. ; Olafson, B. D. ; States, D. J. ; Swaminathan, S. ; Karplus, M. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J. Comput. Chem. 1983, 4, 187–217.
Brooks, B. R. ; Janezic, D. ; Karplus, M. Harmonic analysis of large systems. I. Methodology. J. Comput. Chem. 2004, 16, 1522–1542.
Brooks, W. H. ; McCloskey, D. E. ; Daniel, K. G. ; Ealick, S. E. ; III; Secrist, J. A. ; Waud, W. R. ; Pegg, A. E. ; Guida, W. C. In silico chemical library screening and experimental validation of a novel 9-aminoacridine based lead-inhibitor of human S-adenosylmethionine decarboxylase. J. Chem. Inf. Model. 2007, 47, 1897–1905.
Brown, R. D. ; Martin, Y. C. The information content of 2D and 3D structural descriptors relevant to ligand-receptor binding. J. Chem. Inf. Comput. Sci. 1997, 37, 1–9.
Brown, R. D. ; Martin, Y. C. Use of structure-activity data to compare structure-based clustering methods and descriptors for use in compound selection. J. Chem. Inf. Comput. Sci. 1996, 36, 572–584.
Brown, R. S. Hepatitis C and liver transplantation. Nature 2005, 436, 973–978.
Brown, S. P. ; Muchmore, S. W. High-throughput calculation of protein-ligand binding affinities: modification and adaptation of the MM-PBSA protocol to enterprise grid computing. J. Chem. Inf. Model. 2006, 46, 999–1005.
Brown, S. P. ; Muchmore, S. W. Rapid estimation of relative protein-ligand binding affinities using a high-throughput version of MM-PBSA. J. Chem. Inf. Model. 2007, 47, 1493–1503.
Bruice, T. C. ; Lightstone, F. C. Ground state and transition state contributions to the rates of intramolecular and enzymatic reactions. Acc. Chem. Res. 1999, 32, 127–136.
Bruncko, M. ; et al. Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL. J. Med. Chem. 2007, 50, 641–662.
Brunger, A. T. Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. Nature 1992, 355, 472–474.
Bryce, R. A. ; Hillier, I. H. ; Naismith, J. H. Carbohydrate-protein recognition: molecular dynamics simulations and free energy analysis of oligosaccharide binding to concanavalin a. Biophys J., 2001, 81, 1373–1388.
Bultinck, P. ; Kuppens, T. ; Gironés, X. ; Carbó-Dorca, R. Quantum similarity superposition algorithm (QSSA): a consistent scheme for molecular alignment and molecular similarity based on quantum chemistry. J. Chem. Inf. Comput. Sci. 2003, 43, 1143–1150.
Bursi, R. ; Dao, T. ; van Wijk, T. ; de Gooyer, M. ; Kellenbach, E. ; Verwer, P. Comparative spectra analysis (CoSA): spectra as three-dimensional molecular descriptors for the prediction of biological activities. J. Chem. Inf. Comput. Sci. 1999, 39(5), 861–867.
Bzowska, A. ; Kulikowska, E. ; Darzynkiewicz, E. ; Shugar, D. Purine nucleoside phosphorylase. structure-activity relationships for substrate and inhibitor properties of N-1-, N-7-, and C-8-substituted analogues; differentiation of mammalian and bacterial enzymes with N-1-methylinosine and guanosine. J. Biol. Chem. 1988, 263, 9212–9217.
Cabrera, M. A. ; Gonzalez, I. ; Fernandez, C. ; Navarro, C. ; Bermejo, M. A topological substructural approach for the prediction of P-glycoprotein substrates. J. Pharm. Sci. 2006, 95, 589.
Caflisch, A. ; Miranker, A. ; Karplus, M. Multiple copy simultaneous search and construction of ligands in binding sites: application to inhibitors of HIV-I aspartic proteinase. J. Med. Chem. 1993, 36, 2142–2167.
Carbó-Dorca, R. ; Gironés, X. Foundation of quantum similarity measures and their relationship to QSPR: density function structure, approximations, and application examples. Int. J. Quantum Chem. 2005, 101, 8–20.
Card, G. I. ; Blasdel, I. ; England, B. P. ; Zhang, C. ; Suzuki, Y. ; Gillette, S. ; Fong, D. ; Ibrahim, P. N. ; et al. A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nat. Biotechnol. 2005, 23, 201–207.
Carlson, H. A. ; Masukawa, K. M. ; Rubins, K.; D., B. F. ; Jorgensen, W. L. ; Lins, R. D. ; Briggs, J. M. ; McCammon, J. A. Developing a dynamic pharmacophore model for HIV-1 integrase. J. Med. Chem. 2000, 43, 2100–2114.
Carlson, H. A. ; McCammon, J. A. Accommodating protein flexibility in computational drug design. Mol. Pharmacol. 2000, 57, 213–218.
Carlson, J. ; Fischer, A. Thyroid purine nucleoside phosphorylase. II. Kinetic model by alternate substrate and inhibition studies. Biochim. Biophys. Acta 1979, 566, 259–265.
Caron, G. ; Ermondi, G. ; Testa, B. Predicting the oxidative metabolism of statins: an application of the MetaSite algorithm. Pharm. Res. 2007, 24, 480.
Carr, R. ; Jhoti, H. Structure-based screening of low-affinity compounds. Drug Discov. Today 2002, 7, 522–527.
Cato, S. J. Exploring pharmacophores with CHEM-X. In: Pharmacophore Perception, Development, and Use in Drug Design, Güner, O. F. ; Ed. La Jolla, CA: International University Line; 2000, 110–125.
Cavalli, A. ; Carloni, P. ; Recanatini, M. Target-related applications of first principles quantum chemical methods in drug design. Chem. Rev. 2006, 106, 3497–3519.
Cavalli, A. ; Poluzzi, E. ; De Ponti, F. ; Recanatini, M. Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K+ channel blockers. J. Med. Chem. 2002, 45(18), 3844–3853.
Cavasotto, C. N. ; Orry, A. J. W .; Abagyan, R. A. Structure-Based Identification of Binding Sites, Native Ligands and Potential Inhibitors for G-Protein Coupled Receptors. Proteins 2008, 51, 423.
Cavasotto, C. N. ; Orry, A. J. W. ; Murgolo, N. J. ; Czarniecki, M. F. ; Kocsi, S. A .; Hawes, B. E. ; O'Neill, K. A. ; Hine, H. ; Burton, M. S. ; Voigt, J. H. ; Abagyan, R. A. ; Bayne, M. L. ; Monsma, F. J. Discovery of Novel Chemotypes to a G-Protein-Coupled Receptor through Ligand-Steered Homology Modeling and Structure-Based Virtual Screening. J. Med. Chem. 2008, 51, 581.
Cavasotto, C. N. ; Orry, A. J. W. Ligand docking and structure-based virtual screening in drug discovery. Curr. Top. Med. Chem. 2007, 7, 1006–1014.
Cavasotto, C. N. ; Ortiz, M. A. ; Abagyan, R. A. ; Piedrafita, F. J. In silico identification of novel EGFR inhibitors with antiproliferative activity against cancer cells. Bioorg. Med. Chem. Lett. 2006, 16, 1969–1974.
Chakravarty, S. ; Dugar, S. Inhibitors of p38a MAP kinase. Ann. Rep. Med. Chem. 2002, 37, 177–186.
Chang, C. E. ; et al. Gated binding of ligands to HIV-1 protease: Brownian dynamics simulations in a coarse-grained model. Biophys. J. 2006, 90(11), 3880–3885.
Chang, C. E. ; Potter, M. J. ; Gilson, M. K. Calculation of molecular configuration integrals. J. Phys. Chem. B 2003, 107, 1048–1055.
Chang, C.-E. ; Chen, W. ; Gilson, M. K. Calculation of cyclodextrin binding affinities: energy, entropy, and implications for drug design. Biophys. J. 2004, 87, 3035–3049.
Chang, C.-E. ; Chen, W. ; Gilson, M. K. Ligand configurational entropy and protein binding. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 1534–1539.
Chang, C.-E. A. ; Chen, W. ; Gilson, M. K. Evaluating the accuracy of the quasiharmonic approximation. J. Chem. Theory Comput. 2005, 1(5), 1017–1028.
Chang, C.-E. A. ; Chen, W. ; Gilson, M. K. Ligand configurational entropy and protein binding. Proc. Natl. Acad. Sci. U.S.A. 2007, 104(5), 1534–1539.
Chang, C.-E. A. ; Gilson, M. K. Free energy, entropy, and induced fit in host-guest recognition: calculations with the second-generation mining minima algorithm. J. Am. Chem. Soc. 2004, 126(40), 13156–13164.
Chang, G. ; Guida, W. ; Still, W. C. An internal coordinate Monte Carlo method for searching conformational space. J. Am. Chem. Soc. 1989, 111, 4379–4386.
Chaudry, U. A. ; Popelier, P. L. A. Estimation of pKa using quantum topological molecular similarity descriptors: application to carboxylic acids, anilines and phenols. J. Org. Chem. 2004, 69, 233–241.
Cheatham, T. E. ; Srinivasan, J. ; Case, D. A. ; Kollman, P. A. Molecular dynamics and continuum solvent studies of the stability of polyG-polyC and polyA-polyT DNA duplexes in solution. J. Biomol. Struct. Dyn. 1998, 16, 265–280.
Chen, J. C. ; Xu, S. L. ; Wawrzak, Z. ; Basarab, G. S. ; Jordan, D. B. Structure-based design of potent inhibitors of scytalone dehydratase: displacement of a water molecule from the active site. Biochemistry 1998, 37, 17735–17744.
Chen, K. X. ; Njoroge, F. G. ; Pichardo, J. ; Prongay, A. ; Butkiewicz, N. ; Yao, N. ; Madison, V. ; Girijavallabhan, V. Potent 7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-based macrocyclic inhibitors of hepatitis C virus NS3 protease. J. Med. Chem. 2006, 49, 567–574.
Chen, L. ; Gui, C. ; Luo, X. ; Yang, Q. ; Guenther, S. ; Scandella, E. ; Drosten, C. ; Bai, D. ; He, X. ; Ludewig, B. ; Chen, J. ; Luo, H. ; Yang, Y. ; Yang, Y. ; Zou, J. ; Thiel, V. ; Chen, K. ; Shen, J. ; Shen, X. ; Jiang, H. Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro. J. Virol. 2005, 79, 7095–7103.
Chen, S. H. ; Tan, S. L. Discovery of small-molecule inhibitors of HCV NS3-4A protease as potential therapeutic agents against HCV infection. Curr. Med. Chem. 2005, 12, 2317–2342.
Chen, W. ; Chang, C.-E. A. ; Gilson, M. K. Concepts in receptor optimization: Targeting the rgd peptide. J. Am. Chem. Soc. 2006, 128(14), 4675–4684.
Chen, X. ; Rusinki, A., III ; Tropsha, A. ; Young, S. S. Automated pharmacophore identification for large chemical data sets. J. Chem. Inf. Comput. Sci. 1999, 39, 887–896.
Chen, X. ; Rusinko, A., III ; Young, S. S. Recursive partitioning analysis of a large structure-activity data set using three-dimensional descriptors. J. Chem. Inf. Comput. Sci. 1998, 38, 1054–1062.
Chen, X. H. ; Zhang, J. Z. H. Theoretical method for full ab initio calculation of DNA/RNA-ligand interaction energy. J. Chem. Phys. 2004, 120, 11386–11391.
Chen, X. Y. ; Berti, P. J. ; Schramm, V. L. Ricin A-chain: kinetic isotope effects and transition state structure with stem-loop RNA. J. Am. Chem. Soc. 2000, 122, 1609–1617.
Chen, X. Y. ; Berti, P. J. ; Schramm, V. L. Transition-state analysis for depurination of DNA by ricin A-chain. J. Am. Chem. Soc. 2000, 122, 6527–6534.
Chen, Z. ; Gibson, T. B. ; Robinson, F. ; Silvestro, L. ; Pearson, G. ; Xu, B.-E. ; Wright, A. ; Vanderbilt, C. ; Cobb, M. H. MAP kinases. Chem. Rev. 2001, 101, 2449–2476.
Cherezov, V. ; Rosenbaum, D. M. ; Hanson, M. A. ; Rasmussen, S. G. F .; Thian, F. S. ; Kobilka, T. S. ; Choi, H. J. ; Kuhn, P. ; Weis, W. I. ; Kobilka, B. K. ; Stevens, R. C. High-Resolution Crystal Structure of an Engineered Human β2-Adrenergic G Protein-Coupled Receptor. Science 2007, 318, 1258.
Cherezov, V. ; Rosenbaum, D. M. ; Hanson, M. A. ; Rasmussen, S. G. F. ; Thian, F. S. ; Kobilka, T. S. ; Choi, H.-J. ; Kuhn, P. ; Weis, W. I. ; Kobilka, B. K. ; Stevens, R. C. ; Takeda, S. ; Kadowaki, S. ; Haga, T. ; Takaesu, H. ; Mitaku, S. ; Fredriksson, R. ; Lagerstrom, M. C. ; Lundin, L. G. ; Schioth, H. B. ; Pierce, K. L. ; Premont, R. T. ; Lefkowitz, R. J. ; Lefkowitz, R. J. ; Shenoy, S. K. ; Rosenbaum, D. M. High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor. Science 2007, 318, (5854), 1258–1265.
Chevrier, B. ; Schalk, C. ; D'Orchymont, H. ; Rondeau, J. M. ; Moras, D. ; Tarnus, C. Crystal structure of Aeromonas proteolytica aminopeptidase: a prototypical member of the co-catalytic zinc enzyme family. Structure 1994, 2, 283–291.
Chipot, C. ; Pearlman, D. A. Free energy calculations: the long and winding gilded road. Mol. Simulat. 2002, 28(1–2), 1–12.
Chipot, C. ; Pohorille, A. ; Eds. Free Energy Calculations: Theory and Applications in Chemistry and Biology, Vol. 86. New York: Springer, 2007.
Chipot, C. ; Pohorille, A. In Springer Series in Chemical Physics: Free Energy Calculations: Theory and Applications in Chemistry and Biology, Vol. 86, Chipot, C. ; Pohorille, A. ; Eds. Berlin: Springer-Verlag; 2007, 33–75.
Chipot, C. ; Rozanska, X. ; Dixit, S. B. Can free energy calculations be fast and accurate at the same time? Binding of low-affinity, non-peptide inhibitors to the SH2 domain of the src protein. J. Comput. Aided Mol. Des. 2005, 19, 765–770.
Chipot, C. Free energy calculations in biomolecular simulations: how useful are they in practice? In: Lecture Notes in Computational Science and Engineering: New Algorithms for Molecular Simulation, Leimkuhler, B. ; Chipot, C. ; Elber, R. ; Laaksonen, A. ; Mark, A. E. ; Schlick, T. ; Schütte, C. ; Skeel, R. ; Eds. Vol. 49. New York: Springer, 2005, 183–209.
Cho, A. E. ; Guallar, V. ; Berne, B. J. ; Friesner, R. A. Importance of accurate charges in molecular docking: quantum mechanical/molecular mechanical approach. J. Comp. Chem. 2005, 29, 917–930.
Cho, S. J. ; Zheng, W. ; Tropsha, A. Rational combinatorial library design. 2. Rational design of targeted combinatorial peptide libraries using chemical similarity probe and the inverse QSAR approaches. J. Chem. Inf. Comput. Sci. 1998, 38, 259–268.
Chohan, K. K. ; Paine, S. W. ; Waters, N. J. Quantitative structure activity relationships in drug metabolism. Curr. Top. Med. Chem. 2006, 6, 1569–1578.
Chong, L. ; Duan, Y. ; Wang, L. ; Massova, I. ; Kollman, P. A. Molecular dynamics and free-energy calculations applied to affinity maturation in antibody 48g7. Proc. Natl. Acad. Sci. U.S.A. 1995, 96, 14330–14335.
Chou, J. J. ; Case, D. A. ; Bax, A. Insights into the mobility of methyl-bearing side chains in proteins from (3)J(CC) and (3)J(CN) couplings. J. Am. Chem. Soc. 2003, 125(29), 8959–8966.
Chowdhury, S. F. ; Lucrezia, R. D. ; Guerrero, R. H. ; Brun, R. ; Goodman, J. ; Ruiz-Perez, L. M. ; Pacanowska, D. G. ; Gilbert, I. H. Novel inhibitors of leishmanial dihydrofolate reductase. Bioorg. Med. Chem. Lett. 2001, 11, 977–980.
Cianchetta, G. ; Singleton, R. W. ; Zhang, M. ; Wildgoose, M. ; Giesing, D. ; Fravolini, A. ; Cruciani, G. ; Vaz, R. A pharmacophore hypothesis for P-glycoprotein substrate recognition using GRIND-based 3D-QSAR. J. Med. Chem. 2005, 48, 2927.
Cirillo, P. F. ; Pargellis, C. ; Regan, J. The non-diaryl heterocycle class of p38 MAP kinase inhibitors. Curr. Top. Med. Chem. 2002, 2, 1021–1035.
Ciulli, A. ; Williams, G. ; Smith, A. G. ; Blundell, T. L. ; Abell, C. Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods. J. Med. Chem. 2006, 49, 4992–5000.
Claasen, B. ; Axmann, M. ; Meinecke, R. ; Meyer, B. Direct observation of ligand binding to membrane proteins in living cells by a saturation transfer double difference (STDD) NMR spectroscopy method shows a significantly higher affinity of integrin alpha(IIb)beta3 in native platelets than in liposomes. J. Am. Chem. Soc. 2005, 127, 916–919.
Clackson, T. ; Wells, J. A. A hot spot of binding energy in a hormone-receptor interface. Science 1995, 267, 383–386.
Claeyssens, F. ; Ranaghan, K. E. ; Manby, F. R. ; Harvey, J. N. ; Mulholland, A. J. Multiple high-level QM/MM reaction paths demonstrate transition-state stabilization in chorismate mutase: correlation of barrier height with transition-state stabilization. Chem. Commun. (Camb.) 2005, 40, 5068–5070.
Clark, D. E. ; Jones, G. ; Willett, P. Pharmacophoric pattern matching in files of three-dimensional chemical structures: comparison of conformational searching algorithms for flexible searching. J. Chem. Inf. Comput. Sci. 1994, 34, 197–206.
Clark, D. E. Computational prediction of blood-brain barrier permeation. Ann. Rep. Med. Chem. 2005, 40, 403.
Clark, D. E. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood-brain barrier penetration. J. Pharm. Sci. 1999, 88, 815.
Clark, D. E. What has computer-aided molecular design ever done for drug discovery? Exp. Opin. Drug Discov. 2006, 1(2), 103–110.
Clark, M. ; Guarnieri, F. ; Shkurko, I. ; Wiseman, J. Grand canonical Monte Carlo simulation of ligand-protein binding. J. Chem. Info. Model. 2006, 46(1), 231–242.
Clark, M. ; Guarnieri, F. ; Shkurko, I. ; Wiseman, J. Grand canonical Monte Carlo simulation of ligand-protein binding. J. Med. Inf. Model. 2006, 46, 231–242.
Claussen, H. ; Gastreich, M. ; Apelt, V. ; Greene, J. ; Hindle, S. A. ; Lemmen, C. The FlexX database docking environment: rational extraction of receptor based pharmacophores. Curr. Drug Discov. Technol. 2004, 1, 49–60.
Cleland, W. Isotope Effects: Determination of enzyme transition state structure. Methods Enzymol. 1995, 249, 341–373.
Clement, O. ; Mehl, A.T. In: Pharmacophore Preception, Development, and Use in Drug Design, O. F. Guner , Ed.; La Jolla, CA: International University Line; 2000, 71.
Clinch, K. ; Evans, G. ; Fleet, G. ; Furneaux, R. ; Johnson, S. ; Lenz, D. ; Mee, S. ; Rands, P. ; Schramm, V. ; Taylor Ringia, E. ; Tyler, P. Syntheses and bio-activities of the L-enantiomers of two potent transition state analogue inhibitors of purine nucleoside phosphorylases. Org. Biomol. Chem. 2006, 4, 1131–1139.
Collaborative Computational Project . The CCP4 suite: programs for protein crystallography. Acta Cryst. 1994 D50, 760–763.
Collins, J. R. ; Burt, S. K. ; Erickson, J. W. Flap opening in HIV-1 protease simulated by ‘activated’ molecular dynamics. Nat. Struct. Mol. Biol. 1995, 2(4), 334–338.
Collins, J. R. ; Burt, S. K. ; Erickson, J. W. Flap opening in HIV-1 protease simulated by activated molecular dynamics. Nat. Struct. Biol. 1995, 2(4), 334–338.
Condra, J. H. ; et al. In-vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 1995, 374(6522), 569–571.
Congreve, M. ; Carr, R. ; Murray, C. ; Jhoti, H. A ‘rule of three’ for fragment-based lead discovery? Drug Discov. Today 2003, 8, 876–877.
Congreve, M. ; Carr, R. ; Murray, C. ; Jhoti, H. A “rule of three” for fragment-based lead discovery? Drug Discov. Today 2003, 8, 876–877.
Congreve, M. ; Chessari, G. ; Tisi, D. ; Woodhead A. J. Recent developments in fragment based drug discovery. J. Med. Chem. 2008, 51, in press.
Congreve, M. ; Chessari, G. ; Tisi, D. ; Woodhead, A. J. Recent developments in fragment-based drug discovery. J. Med. Chem. 2008, 51, 3661–3680.
Congreve, M. ; Chessari, G. ; Tisi, D. ; Woodhead, A. J. Recent developments in fragment-based drug discovery. J. Med. Chem. 2008, 51, 3661–3680.
Congreve, M. ; et al. Application of fragment screening by x-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase. J. Med. Chem. 2007, 50, 1124–1132.
Corbeil, C. R. ; Englebienne, P. ; Yannopoulos, C. G. ; Chan, L. ; Das, S. K. ; Bilimoria, D. ; L'Heureux, L. ; Moitessier, N. Docking ligands into flexible and solvated macromolecules. 2. Development and application of FITTED 1.5 to the virtual screening of potential HCV polymerase inhibitors. J. Chem. Inf. Model. 2008, 48, 902–909.
Cornell, W. D. ; Cieplak, P. ; Bayly, C. I. ; Gould, I. R. ; Merz, K. M. ; Ferguson, D. M. ; Spellmeyer, D. C. ; Fox, T. ; Caldwell, J. W. ; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc. 1995, 117(19), 5179–5197.
Cornell, W. D. ; Cieplak, P. ; Bayly, C. I. ; Gould, I. R. ; Merz, K. M., Jr. ; Ferguson, D. M. ; Spellmeyer, D. C. ; Fox, T. ; Caldwell, J. W. ; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc. 1995, 117(19), 5179–5197.
Cornell, W. D. Recent evaluations of high throughput docking methods for pharmaceutical lead finding: consensus and caveats. Annu. Rep. Comp. Chem. 2006, 2, 297–323.
Costanzi, S . On the Applicability of GPCR Homolgy Models to Computer-Aided Drug Discovery: A Comparison between In Silico and Crystal Structures of the β2-Adrenergic Receptor. J. Med. Chem. 2008, 51, 2907.
Coulson, C. A. Coulson is credited with using this analogy to describe the accuracy required to compute the energy of interaction between two molecules.
Coupez, B. ; Lewis, R. A. Docking and scoring: theoretically easy, practically impossible? Curr. Med. Chem. 2006, 13, 2995–3003.
Cournia, Z. ; Leng, L. ; Gandavadi, S. ; Du, X. ; Bucala, R. ; Jorgensen, W. L. Discovery of human macrophage migration inhibitory factor (MIF)-CD74 antagonists via virtual screening. J. Med. Chem. 2009, 52, 416–424.
Cozza, G. ; Bonvini, P. ; Zorzi, E. ; Poletto, G. ; Pagano, M. A. ; Sarno, S. ; Donella-Deana, A. ; Zagotto, G. ; Rosolen, A. ; Pinna, L. A. ; Meggio, F. ; Moro, S. Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application. J. Med. Chem. 2006, 49, 2363–2366.
Cramer III, R. D. ; Patterson, D. E. ; Bunce, J. D. Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 1988, 110, 5959–5967.
Cramer, R. D. ; Patterson, D. E. ; Bunce, J. D. Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 1988, 110, 5959–5967.
Crippen, C. M. ; Havel, T. F. Distance Geometry and Molecular Conformation. New York, NY: John Wiley & Sons; 1988.
Crippen, C. M. ; Havel, T. F. Distance Geometry and Molecular Conformation. New York, NY: Wiley; 1988.
Crivori, P. ; Reinach, B. ; Pezzetta, D. ; Poggesi, I. Computational models for identifying potential P-glycoprotein substrates and inhibitors. Mol. Pharm. 2006, 3, 33.
Crivori, P. ; Zamora, I. ; Speed, B. ; Orrenius, C. ; Poggesi, I. Model based on GRID-derived descriptors for estimating CYP3A4 enzyme stability of potential drug candidates. J. Comput. Aided Mol. Des. 2004, 18, 155.
Crooks, G. E. Path-ensemble averages in systems driven far from equilibrium. Phys. Rev. E 2000, 61(3), 2361–2366.
Crozier, P. S. ; Stevens, M. J. ; Forrest, L. R. ; Woolf, T. B. Molecular Dynamics Simulation of Dark-adapted Rhodopsin in an Explicit Membrane Bilayer: Coupling between Local Retinal and Larger Scale Conformational Change. J. Mol. Biol. 2003, 333, 493.
Cruciani, G. ; Carosati, E. ; De Boeck, B. ; Ethirajulu, K. ; Mackie, C. ; Howe, T. ; Vianello, R. MetaSite: understanding metabolism in human cytochromes from the perspective of the chemist. J. Med. Chem. 2005, 48, 6970.
Cruickshank, D. W. J. Remarks about protein structure precision. Acta Crystallogr., Sect. D 1999, D55, 583–601.
Cui, G. ; Wang, B. ; Merz, K. M., Jr. Computational studies of the farnesyltransferase ternary complex part I: substrate binding. Biochemistry 2005, 44(50), 16513–16523.
Cui, G. ; Xue, L. ; Merz, J., K. M. Understanding the substrate selectivity and the product regioselectivity of orf2-catalyzed aromatic prenylations. Biochemistry 2006, submitted.
Cummings, M. D. ; DesJarlais, R. L. ; Gibbs, A. C. ; Mohan, V. ; Jaeger, E. P. Comparison of automated docking programs as virtual screening tools. J. Med. Chem. 2005, 48(4), 962–976.
Cummings, M. D. ; DesJarlais, R. L. ; Gibbs, A. C. ; Mohan, V. ; Jaeger, E. P. Comparison of automated docking programs as virtual screening tools. J. Med. Chem. 2005, 48, 962–976.
Curtiss, L. A. ; Raghavachari, K. ; Redfern, P. C. ; Rassolov, V. ; Pople, J. A. Gaussian-3 (G3) theory for molecules containing first and second-row atoms. J. Chem. Phys. 1998, 109(18), 7764–7776.
Curtiss, L. A. ; Redfern, P. C. ; Raghavachari, K. ; Pople, J. A. Gaussian-3X (G3X) theory: use of improved geometries, zero-point energies, and Hartree-Fock basis sets. J. Chem. Phys. 2001, 114(1), 108–117.
Daggett, V. Long timescale simulations. Curr. Opin. Struc. Biol. 2000, 10, 160–164.
Dalvit, C. ; et al. High-throughput NMR-based screening with competition binding experiments. J. Am. Chem. Soc. 2002, 124, 7702–7709.
Dalvit, C. ; et al. Identification of compounds with binding affinity to proteins via magnetization transfer from bulk water. J. Biomol. NMR 2000, 18, 65–68.
Dalvit, C. ; Fogliatto, G. ; Stewart, A. ; Veronesi, M. ; Stockman, B. WaterLOGSY as a method for primary NMR screening: practical aspects and range of applicability. J. Biomol. NMR 2001, 21, 349–359.
Dambach, D. M. Potential adverse effects associated with inhibition of p38. α/β MAP kinases Curr. Top. Med. Chem. 2005, 5, 929–939.
Damm, K. L. ; Ung, P. M. ; Quintero, J. J. ; Gestwicki, J. E. ; Carlson, H. A. A poke in the eye: inhibiting HIV-1 protease through its flap-recognition pocket. Biopolymers 2008, 89, 643–652.
Das, J. ; Moquin, R. V. ; Pitt, S. ; Zhang, R. ; Shen, D. R. ; McIntyre, K. W. ; Gillooly, K. M. ; Doweyko, A. M. ; Sack, J. S. ; Zhang, H. ; Kiefer, S. E. ; Kish, K. F. ; McKinnon, M. ; Barrish, J. C. ; Dodd, J. ; Schieven, G. L. ; Lefterheris, K. Pyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38α inhibitors. Bioorg. Med. Chem. Lett. 2008, 18, 2652–2657.
Das, K. ; Clark, A. D., Jr. ; Lewi, P. J. ; Heeres, J. ; de Jonge, M. R. ; Koymans, L. M. H. ; Vinkers, H. M. ; Daeyaert, F. ; Ludovici, D. W. ; Kukla, M. J. ; De Corte, B. ; Kavash, R. W. ; Ho, C. Y. ; Ye, H. ; Lichtenstein, M. A. ; Andries, K. ; Pauwels, R. ; de Béthune, M.-P. ; Boyer, P. L. ; Clark, P. ; Hughes, S. H. ; Janssen, P. A. J. ; Arnold, E. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (Etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J. Med. Chem. 2004, 47, 2550–2560.
Davis, A. M. ; St. Gallay, S. A. ; Gerard, J. K. Limitations and lessons in the use of X-ray structural information in drug design. Drug Discov. Today 2008, 13, 831–841.
Davis, A. M. ; Teague, S. J. ; Kleywegt, G. J. Application and limitations of X-ray crystallographic data in structure-based ligand and drug design. Angew. Chem. Int. Ed. Engl. 2003, 42(24), 2718–2736.
Davis, A. M. ; Teague, S. J. ; Kleywegt, G. J. Application and limitations of X-ray crystallographic data in structure-based ligand and drug design. Angew. Chem. Int. Ed. Engl. 2003, 42(24), 2718–2736.
Day, G.M. ; Motherwell, W. D. S. ; Ammon, H. L. ; Boerrigter, S. X. M. ; Della Valle, R. G. ; Venuti, E. ; Dzyabchenko, A. ; Dunitz, J. D. ; Schweizer, B. ; van Eijck, B. P. ; Erk, P. ; Facelli, J. C. ; Bazterra, V. E. ; Ferraro, M. B. ; Hofmann, D. W. M. ; Leusen, F. J. J. ; Liang, C. ; Pantelides, C. C. ; Karamertzanis, P. G. ; Price, S. L. ; Lewis, T. C. ; Nowell, H. ; Torrisi, A. ; Scheraga, H. A. ; Arnautova, Y. A. , Schmidt, M. U. ; and Verwer, P. . A third blind test of crystal structure prediction. Acta Crystall. B-Struc., 2005, 61(5), 511–527.
de Cerqueira, L. P. ; Golbraikh, A. ; Oloff, S. ; Xiao, Y. ; Tropsha, A. Combinatorial QSAR modeling of P-glycoprotein substrates. J. Chem. Inf. Model. 2006, 46, 1245–1254.
de Graaf, C. ; Oostenbrink, C. ; Keizers, P. H. J. ; van Vugt-Lussenburg, B. M. A. ; Commandeur, J. N. M. ; Vermeulen, N. P. E. Free energies of binding of R- and S- propranolol to wild-type and f483a mutant cytochrome p450 d26 from molecular dynamics simulations. Eur. Biophys. J. 2007, 36(6), 589–599.
de Lima, P. ; Golbraikh, A. ; Oloff, S. ; Xiao, Y. ; Tropsha, A. Combinatorial QSAR modeling of P-glycoprotein substrates. J. Chem. Inf. Model. 2006, 46, 1245.
De Simone, A. ; Dobson, G. G. ; Verma, C. S. ; Zagari, A. ; Fraternali, F. Prion and water: tight and dynamical hydration sites have a key role in structural stability. Proc. Natl. Acad. Sci. U.S.A. 2005, 102(21), 7535–7540.
Deconinck, E. ; Hancock, T. ; Coomans, D. ; Massart, D. L. ; Vander Heyden, Y. Classification of drugs in absorption classes using the classification and regression trees (CART) methodology. J. Pharm. Biomed. Anal. 2005, 39, 91–103.
Delaney, J. S. Predicting aqueous solubility from structure. Drug Discov. Today 2005, 10, 289.
Delisle, R. K. ; Lowrie, J. F. ; Hobbs, D. W. ; Diller, D. J. Computational ADME/Tox modeling: aiding understanding and enhancing decision making in drug design. Curr. Comput. Aided Drug Des. 2005, 1, 325.
Deng Y. ; Roux, B. Computation of binding free energy with molecular dynamics and grand canonical Monte Carlo simulations. J. Chem. Phys. 2008, 128(11).
Deng, J. ; Lee, K. W. ; Sanchez, T. ; Cui, M. ; Neamati, N. ; Briggs, J. M. Dynamic receptor-based pharmacophore model development and its application in designing novel HIV-1 integrase inhibitors. J. Med. Chem. 2005, 48, 1496–1505.
Deng, Q. ; Lu, Z. ; Bohn, J. ; Ellsworth, K. P. ; Myers, R. W. ; Geissler, W. M. ; Harris, G .; Willoughby, C. A. ; Chapman, K. ; Mckeever, B. ; Mosley, R. Modeling aided design of potent glycogen phosphorylase inhibitors. J. Mol. Graph. Model. 2005, 23, 457–464.
Deng, Y. ; Roux B. Calculation of standard binding free energies: aromatic molecules in the T4 lysozyme l99A mutant. J. Chem. Theory Comput. 2006, 2, 1255–1273.
Deng, Y. ; Roux, B. Computations of standard binding free energies with molecular dynamics simulations. J. Phys. Chem. B 2008, in press.
DesJarlais, R. L. ; Cummings, M. D. ; Gibbs, A. C. Virtual docking: how are we doing and how can we improve? Front. Drug Des. Discov. 2007, 3, 81–103.
Desmarais, W. ; Bienvenue, D. L. ; Bzymek, K. P. ; Petsko, G. A. ; Ringe, D. ; Holz, R. C. J. The high-resolution structures of the neutral and the low pH crystals of aminopeptidase from Aeromonas proteolytica . Biol. Inorg. Chem. 2006, 11, 398–408.
Devillers, J. Strengths and weaknesses of the back propagation neural network in QSAR and QSPR studies. In: Genetic Algorithms in Molecular Modeling, Devillers, J. ; Ed. San Diego, CA: Academic Press; 1996; 1–24.
Dewar, M. J. S. ; Thiel, W. Ground states of molecules. 39. MNDO results for molecules containing hydrogen, carbon, nitrogen, and oxygen. J. Am. Chem. Soc. 1977, 99(15), 4907–4917.
Dewar, M. J. S. ; Zoebisch, E. G. ; Healy, E. F. ; Stewart, J. J. P. AM1: a new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 1985, 107, 3902–3909.
Dewar, M. J. S. ; Zoebisch, E. G. ; Healy, E. F. ; Stewart, J. J. P. Development and use of quantum mechanical molecular models. 76. AM1: a new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 1985, 107(13), 3902–3909.
Dhagat, U. ; Carbone, V. ; Chung, R. P.-T.; Matsunaga, T. ; Endo, S. ; Hara, A. ; El-Kabbani, O. A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20α-hydroxysteroid dehydrogenase. Med. Chem. 2007, 3, 546–550.
Dhar, T. G. M. ; Wrobleski, S. T. ; Lin, S. ; Furch, J. A. ; Nirschl, D. S. ; Fan, Y. ; Todderud, G. ; Pitt, S. ; Doweyko, A. M. ; Sack, J. S. ; Mathur, A. ; McKinnon, M. ; Barrish, J. C. ; Dodd, J. H. ; Schieven, G. L. ; Leftheris, K. Synthesis and SAR of p38α MAP kinase inhibitors based on heterobicyclic scaffolds. Bioorg. Med. Chem. Lett. 2007, 17, 5019–5024.
Diabetes overview, National Diabetes Statistics. Fact Sheet, 2005.
Diabetes, World Health Organization. Fact Sheet No. 312, 2006.
Diaz, N. ; Suarez, D. ; Merz, K. M., Jr. ; Sordo, T. L. Molecular dynamics simulations of the TEM-1 beta-lactamase complexed with cephalothin. J. Med. Chem. 2005, 48(3), 780–791.
Dill, K. A. ; Ozkan, S. B. ; Shell, M. S. ; Weikl, T. R. The protein folding problem. Annu. Rev. Biophys. 2008, 37, 289–316.
Dill, K. A. Additivity principles in biochemistry. J. Biol. Chem. 1997, 272, 701–704.
Ding, F. ; Layten, M. ; Simmerling, C. Solution structure of HIV-1 protease flaps probed by comparison of molecular dynamics simulation ensembles and EPR experiments. J. Am. Chem. Soc. 2008, 130 (23), 7184–7185.
Dixit, S. B. ; Chipot, C. Can absolute free energies of association be estimated from molecular mechanical simulations? The biotin-streptavidin system revisited. J. Phys. Chem. A 2001, 105(42), 9795–9799.
Dixon, S. ; Merz, K. M., Jr. ; Lauri, G. ; Ianni, J. C. QMQSAR: utilization of a semiempirical probe potential in a field-based qsar method. J. Comput. Chem. 2005, 26, 23–34.
Dixon, S. L. ; Koehler, R. T. The hidden component of size in two-dimensional fragment descriptors: side effects on sampling in bioactive libraries. J. Med. Chem. 1999, 42, 2287–2900.
Dixon, S. L. ; Merz, K. M. Fast, accurate semiempirical molecular orbital calculations for macromolecules. J. Chem. Phys. 1997, 107(3), 879–893.
Dixon, S. L. ; Merz, K. M. Semiempirical molecular orbital calculations with linear system size scaling. J. Chem. Phys. 1996, 104(17), 6643–6649.
Dixon, S. L. ; Smondyrev, A. M. ; Knoll, E. H. ; Rao, S. N. ; Shaw, D. E. ; Friesner, R. A. PHASE: a new engine for pharmacophore perception, 3D QSAR model development, and 3d database screening. 1. Methodology and preliminary results. J. Comput. Aided Mol. Des. 2006, 20, 647–671.
Dixon, S. L. ; Villar, H. O. Investigation of classification methods for the prediction of activity in diverse chemical libraries. J. Comput. Aided Mol. Des. 1999, 13, 533–545.
Dmytro Kovalskyy , Dubyna, V. ; Mark, A. E. ; Kornelyuk, A. A molecular dynamics study of the structural stability of HIV-1 protease under physiological conditions: the role of Na+ ions in stabilizing the active site. Proteins 2005, 58(2), 450–458.
Doddareddy, M. R. ; Cho, Y. S. ; Koh, H. Y. ; Kim, D. H. ; Pae, A. N. In silico renal clearance model using classical Volsurf approach. J. Chem. Inf. Model. 2006, 46, 1312.
Dolenc, J. ; Oostenbrink, C. ; Koller, J. ; van Gunsteren, W. F. Molecular dynamics simulations and free energy calculations of netropsin and distamycin binding to an aaaaa DNA binding site. Nucleic Acids Res. 2005, 33(2), 725–733.
Doman, T. N. ; McGovern, S. L. ; Witherbee, B. J. ; Kasten, T. P. ; Kurumbail, R. ; Stallings, W. C. ; Connolly, D. T. ; Shoicht, B. K. Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine phosphatase-1B. J. Med. Chem. 2002, 45, 2213–2221.
Dombroski, M. A. ; Letavic, M. A. ; McClure, K. F. ; Barberia, J. T. ; Carty, T. J. ; Cortina, S. R. ; Csiki, C. ; Dipesa, A. J. ; Elliott, N. C. ; Gabel, C. A. ; Jordan, C. K. ; Labasi, J. M. ; Martin, W. H. ; Peese, K. M. ; Stock, I. A. ; Svensson, L. ; Sweeney, F. J. ; Yu, C. H. Benzimidazolone p38 inhibitors. Bioorg. Med. Chem. Lett. 2004, 14, 919–923.
Donini, O. ; Kollman, P. A. Calculation and prediction of binding free energies for the matrix metalloproteinases. J. Med. Chem. 2000, 43, 4180–4188.
Donnini, S. ; Juffer, A. H. Calculations of affinities of peptides for proteins. J. Comput. Chem. 2004, 25, 393–411.
Dooley, A. J. ; Shindo, N. ; Taggart, B. ; Park, J-.G. ; Pang, Y-.P. From genome to drug lead: identification of a small-molecule inhibitor of the SARS virus. Bioorg. Med. Chem. Lett. 2006, 16, 830–833.
Doweyko, A. M. ; Wrobleski, S. T. A comparison of p38 inhibitor-protein structures. Am. Drug Discov. 2006, 1, 47–52.
Doweyko, A. M. QSAR: dead or alive? J. Comput. Aided. Mol. Des. 2008, 22, 81–89.
Dror, O. ; Shulman-Peleg, A. ; Nussov, R. ; Wolfson, H. J. Predicting molecular interaction in silico. I. A guide to pharmacophore identification and its applications to drug design. Curr. Med. Chem. 2004, 11, 71–90.
DSSTox . http://www.epa.gov/nheerl/dsstox/About.html. 2005.
Dumas, J. ; Sibley, R. ; Riedl, B. ; Monahan, M. K. ; Lee, W. ; Lowinger, T. B. ; Redman, A. M. ; Johnson, J. S. ; Kingery-Wood, J. ; Scott, W. J. ; Smith, R. A. ; Bobko, M. ; Schoenleber, R. ; Ranges, G. E. ; Housley, T. J. ; Bhargava, A. ; Wilhelm, S. M. ; Shrikhande, A. Discovery of a new class of p38 kinase inhibitors. Bioorg. Med. Chem. Lett. 2000, 10, 2047–2050.
Dumas, J. ; Smith, R. A. ; Lowinger, T. B. Recent developments in the discovery of protein kinase inhibitors from the urea class. Curr. Opin. Drug Discov. Dev. 2004, 7, 600–616.
Duvic, M. ; Foss, F. M. Mycosis fungoides: pathophysiology and emerging therapies. Semin. Oncol. 2007, 34, S21–28.
Duvic, M. Systemic monotherapy vs combination therapy for ctcl: rationale and future strategies. Oncology 2007, 21, 33–40.
Dvir, H. ; Harel, M. ; McCarthy, A. A. ; Toker, L. ; Silman, I. ; Futerman, A. H. ; Sussman, J. X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease. L. EMBO Rep. 2003, 4, 704–709.
Ealick, S. ; Rule, S. ; Carter, D. ; Greenhough, T. ; Babu, Y. ; Cook, W. ; Habash, J. ; Helliwell, J. ; Stoeckler, J. ; Parks, R. J. Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 Å resolution. J. Biol. Chem. 1990, 265, 1812–1820.
Edwards, P. D. ; et al. Application of fragment-based lead generation to the discovery of novel, cyclic amidine beta-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency. J. Med. Chem. 2007, 50, 5912–5925.
Egan, W. J. ; Lauri, G. Prediction of intestinal permeability. Adv. Drug Deliv. Rev. 2002, 54, 273.
Egan, W. J. ; Merz, K. M. ; Baldwin, J. J. Prediction of drug absorption using multivariate statistics. J. Med. Chem. 2000, 43, 3867.
Egan, W. J. ; Merz, K. M., Jr. ; Baldwin, J. J. Prediction of drug absorption using multivariate statistics. J. Med. Chem. 2000, 43, 3867–3877.
Egan, W. J. ; Walters, W. P. ; Murcko, M. A. Guiding molecules towards drug-likeness. Curr. Opin. Drug Discov. Devel. 2002, 5, 540.
Ehrlich, P. Present status of chemotherapy. Chem. Ber. 1909, 42, 17–47.
Eisenmesser, E. Z. ; Bosco, D. A. ; Akke, M. ; Kern, D. Enzyme dynamics during catalysis. Science 2002, 295(5559), 1520–1523.
Ekroos, M. ; Sjoegren, T. Structural basis for ligand promiscuity in cytochrome P 450 3A4. Proc. National Acad. Sci. U.S.A. 2006, 103, 13682.
Engels, M. F. M. ; Wouters, L. ; Verbeeck, R. ; Vanhoof, G. Outlier mining in high throughput screening experiments. J. Biomol. Screen. 2002; (7): 341–351.
Engh, R. A. ; Huber, R. Accurate bond and angle parameters for X-ray protein structure refinement. Acta Crystallogr. D. Biol. Crystallogr. 1991, 47, 392–400; and Engh, R. A.; Huber, R. Bond lengths and angles of peptide backbone fragments. In: Structure Quality and Target Parameters, International Tables of Crystallography, Vol. F, Rossman, M. G.; Arnold, E.; Eds. Dordrecht: Kluwer, 2001, 382–392.
Engh, R. A. ; Huber, R. Accurate bond and angle parameters for x-ray protein-structure refinement. Acta Crystallogr. A 1991, 47, 392–400.
Enyedy, I. J. ; Lee, S.-L. ; Kuo, A. H. ; Dickson, R. B. ; Lin, C.-L. ; Wang, S. Structure-based approach for the discovery of bis-benzamidines as novel inhibitors of matriptase. J. Med. Chem. 2001, 44, 1349–1355.
Enyedy, I. J. ; Ling, Y. ; Nacro, K. ; Tomita, Y. ; Wu, X. ; Cao, Y. ; Guo, R. ; Li, B. ; Zhu, X. ; Huang, Y. ; Long, Y.-Q. ; Roller, P. P. ; Yang, D. ; Wang, S. Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening. J. Med. Chem. 2001, 44, 4313–4234.
Enyedy, I.; Egan, W. Can we use docking and scoring for hit-to-lead optimization? J. Comput. Aided Mol. Des. 2008.
Eriksson, A. E. ; Baase, W. A. ; Matthews, B. W. Similar hydrophobic replacements of leu99 and phe153 within the core of T4 lysozyme have different structural and thermodynamic consequences. J. Mol. Biol. 1993, 229, 747–769.
Eriksson, A. E. ; Baase, W. A. ; Zhang, X. J. ; Heinz, D. W. ; Blaber, M. ; Baldwin; E. P. ; Matthews, B. W. Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect. Science 1992, 255, 178–183.
Erion, M. D. ; Dang, Q. ; Reddy, M. R. ; Kasibhatla, S. R. ; Huang, J. ; Lipscomb, W. N. ; van Poelje, P. D. Structure-guided design of amp mimics that inhibit fructose-1,6-bisphosphatase with high affinity and specificity. J. Am. Chem. Soc. 2007, 129, 15480–15490.
Erion, M. D. ; Stoeckler, J. D. ; Guida, W. C. ; Walter, R. L. ; Ealick, S. E. Purine nucleoside phosphorylase. 2. Catalytic mechanism. Biochemistry 1997, 36, 11735–11748.
Erlanson, D. A. ; Wells, J. A .; Braisted, A. C. TETHERING: Fragment-Based Drug Discovery. Annu. Rev. Biophys. Struct. 2004, 33, 199.
Essex, J. W. ; Severance, D. L. ; Tirado-Rives, J. ; Jorgensen, W. L. Monte Carlo simulations for proteins: binding affinities for trypsin-benzamidine complexes via free energy perturbations. J. Phys. Chem. 1997, 101, 9663–9669.
Estrada, E. ; Patlewicz, G. On the usefulness of graph-theoretic descriptors in predicting theoretical parameters: phototoxicity of polycyclic aromatic hydrocarbons (PAHs). Acta Clin. Croat. 2004, 77, 203–211.
Estrada, E. ; Uriarte, E. ; Molina, E. ; Simon-Manso, Y. ; Milne, G. W. A. An integrated in silico analysis of drug-binding to human serum albumin. J. Chem. Inf. Model. 2006, 46, 2709.
Evans, G. ; Furneaux, R. ; Hutchison, T. ; Kezar, H. ; Morris, P. J. ; Schramm, V. ; Tyler, P. Addition of lithiated 9-deazapurine derivatives to a carbohydrate cyclic imine: convergent synthesis of the aza-C-nucleoside Immucillins. J. Org. Chem. 2001, 66, 5723–5730.
Evans, G. ; Furneaux, R. ; Lewandowicz, A. ; Schramm, V. ; Tyler, P. Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase. J. Med. Chem. 2003, 46, 3412–3423.
Evans, G. ; Furneaux, R. ; Lewandowicz, A. ; Schramm, V. ; Tyler, P. Synthesis of second-generation transition state analogues of human purine nucleoside phosphorylase. J. Med. Chem. 2003, 46, 5271–5276.
Evans, G. ; Furneaux, R. ; Tyler, P. ; Schramm, V. Synthesis of a transition state analogue inhibitor of purine nucleoside phosphorylase via the mannich reaction. Org. Lett. 2003, 5, 3639–3640.
Evans, G. B. ; Furneaux, R. H. ; Gainsford, G. J. ; Schramm, V. L. ; Tyler, P. C. Synthesis of transition state analogue inhibitors for purine nucleoside phosphorylase and N-riboside hydrolases. Tetrahedron 2000, 56, 3053–3062.
Evers, A ; Klabunde, T . Structure-based Drug Discovery Using GPCR Homology Modeling: Successful Virtual Screening for Antagonists of the Alpha1A Adrenergic Receptor. J. Med. Chem. 2005, 48, 1088.
Faller, B. ; Wang, J. ; Zimmerlin, A. ; Bell, L. ; Hamon, J. ; Whitebread, S. ; Azzaoui, K. ; Bojanic, D. ; Urban, L. High-throughput in vitro profiling assays: lessons learnt from experiences at Novartis. Expert Opin. Drug Metab. Tox. 2006, 2, 823.
FDA . http://www.fda.gov/cder/Offices/OPS_IO/. 2005.
Feder, M. ; Purta, E. ; Koscinski, L. ; Cubrilo, S. ; Vlahovicek, G. M. ; Bujnicki, J. M. Virtual screening and experimental verification to identify potential inhibitors of the ErmC methyltransferase responsible for bacterial resistance against macrolide antibiotics. ChemMedChem 2008, 3, 316–322.
Fedorov, A. ; Shi, W. ; Kicska, G. ; Fedorov, E. ; Tyler, P. ; Furneaux, R. ; Hanson, J. ; Gainsford, G. ; Larese, J. ; Schramm, V. ; Almo, S. Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis. Biochemistry 2001, 40, 853–860.
Fedorov, D. G. ; Kitaura, K. Extending the power of quantum chemistry to large systems with the fragment molecular orbital method. J. Phys. Chem. A 2007, 111, 6904–6914.
Feig, M. ; Onufriev, A. ; Lee, M. S. ; Im, W. ; Case, D. A. ; Brooks, C. L., III . Performance comparison of generalized Born and Poisson methods in the calculation of electrostatic solvation energies for protein structures. J. Comput. Chem. 2004, 25, 265–284.
Fejzo, J. ; et al. The SHAPES strategy: an NMR-based approach for lead generation in drug discovery. Chem. Biol. 1999, 6, 755–769.
Fejzo, J. ; Lepre, C. ; Xie, X. Applications of NMR screening in drug discovery. Curr. Top. Med. Chem. 2002, 2, 1349–1364.
Feng, B. Y. ; Simeonov, A. ; Jadhav, A. ; Babaoglu, K. ; Inglese, J. ; Shoichet, B. K. ; Austin, C. P. A high-throughput screen for aggregation-based inhibition in a large compound library. J. Med. Chem. 2007, 50, 2385–2390.
Ferrara, P. ; Gohlke, H. ; Price, D. J. ; Klebe, G. ; Brooks, C. L., III . Assessing scoring functions for protein-ligand interactions. J. Med. Chem. 2004, 47, 3032–3047.
Ferrari, A. M. ; Wei, B. Q. ; Costantino, L. ; Shoichet, B. K. Soft docking and multiple receptor conformations in virtual screening. J. Med. Chem. 2004, 47, 5076–5084.
Ferrenberg, A. M. ; Swendsen, R. H. Optimized Monte Carlo data analysis. Phys. Rev. Lett. 1989, 63(12), 1195–1198.
Ferro, D. ; Hermans, J. A. A different best rigid-body molecular fit routine. Acta Crystallogr. 1977, A33, 345–347.
Fersht, A. Enzyme Structure and Mechanism, 2nd ed. New York: Freeman & Co.; 1985.
Fersht, A. R. ; Daggett, V. Protein folding and unfolding at atomic resolution. Cell 2002, 108, 1–20.
Filmore, D. It's a GPCR world Mod. Drug Discov. 2004, 7, 47–48.
Fink, T. ; Bruggesser, H. ; Reymond, J.-L. Virtual exploration of the small molecule chemical universe below 160 daltons. Angew. Chem. Int. Ed. 2005, 44, 1504–1508.
Fink, T. ; Reymond, J. L. Virtual exploration of the chemical universe up to 11 atoms of C, N, O, F: assembly of 26.4 million structures (110.9 million stereoisomers) and analysis for new ring systems, stereochemistry, physicochemical properties, compound classes, and drug discovery. J. Chem. Inf. Model 2007, 47, 342–353.
Fitzpatrick, P. A. ; Steinmetz, A. C. U. ; Ringe, D. ; Klibanov, A. M. Enzyme crystal structure in a neat organic solvent. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 8653–8657.
Fleisher, D. ; Bong, R. ; Stewart, B. H. Improved oral drug delivery: solubility limitations overcome by the use of prodrugs. Adv. Drug Deliv. Rev. 1996, 19(2), 115–130.
Floriano, W. B. ; Vaidehi, N. ; Goddard, W. A. ; Singer, M. S. ; Shepherd, G. M. Molecular mechanisms underlying differential odor responses of a mouse olfactory receptor. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 10712.
Flower, D. R. On the properties of bit string-based measures of chemical similarities. J. Chem. Inf. Comput. Sci. 1998, 38, 379–386.
Foloppe, N. ; Fisher, L. M. ; Howes, R. ; Kierstan, P. ; Potter, A. ; Robertson, A. G. ; Surgenor, A. E. Structure-based design of novel CHK1 inhibitors: insights into hydrogen bonding and protein-ligand affinity. J. Med. Chem. 2005, 48, 4332–4345.
Forbes, I. T. ; Dabbs, S. ; Duckworth, M. D. ; Ham, P. ; Jones, G. E. ; King, F. D. ; Saunders, D. V. ; Blaney, F. E. ; Naylor, C. B. ; Baxter, G. S. ; Blankburn, T. P. ; Kennett, G. A. ; Wood, M. D. Synthesis, biological activity, and molecular modeling studies of selective 5-HT2C/2B receptor antagonists. J. Med. Chem. 1996, 39, 4966–4977.
Forino, M. ; Jung, D. ; Easton, J. B. ; Houghton, P. J. ; Pellecchia, M. Virtual docking approaches to protein kinase B inhibition. J. Med. Chem. 2005, 48, 2278–2281.
Foulkes-Murzycki, J. E. ; Scott, W. R. P. ; Schiffer, C. A. Hydrophobic sliding: a possible mechanism for drug resistance in human immunodeficiency virus type 1 protease. Structure 2007, 15(2), 225–233.
Fowler, P. W. ; Geroult, S. ; Jha, S. ; Waksman, G. ; Coveney, P. V. Rapid, accurate, and precise calculation of relative binding affinities for the SH2 domain using a computational grid. J. Chem. Theory Comput. 2007, 3(3), 1193–1202.
Fowler, P. W. ; Jha, S. ; Coveney, P. V. Grid-based steered thermodynamic integration accelerates the calculation of binding free energies. Philos. T. R. Soc. B., 2005, 363, 1999–2015.
Freedberg, D. I. ; et al. Rapid structural fluctuations of the free HIV protease flaps in solution: relationship to crystal structures and comparison with predictions of dynamics calculations. Protein Sci. 2002, 11(2), 221–232.
Freedberg, D. I. ; et al. Rapid structural fluctuations of the free HIV protease flaps in solution: relationship to crystal structures and comparison with predictions of dynamics calculations. Protein Sci. 2002, 11(2), 221–232.
Frenkel, D. ; Smit, B. Understanding Molecular Simulation: from Algorithms to Applications. San Diego, CA: Academic Press; 2002.
Frey, J. A. ; Leutwyler, S. An ab initio benchmark study of hydrogen bonded formamide dimers. J. Phys. Chem. A 2006, 110(45), 12512–12518.
Freymann, D. M. ; Wenck, M. A. ; Engel, J. C. ; Feng, J. ; Focia, P. J. ; Eakin, A. E. ; Craig, S. P., III . Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi . Chem. Biol. 2000, 7, 957–968.
Friedman, J. H. Multivariate adaptive regression splines. Ann. Stat. 1991, 19, 1–67.
Friesner, R. A. ; Banks, J. L. ; Murphy, R. B. ; Halgren, T. A. ; Klicic, J. J. ; Mainz, D. T. ; Repasky, M. P. ; Knoll, E. H. ; Shelley, M. ; Perry, J. K. ; Shaw, D. E. ; Francis, P. ; Shenkin, P. S. GLIDE: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 2004, 47, 1739–1749.
Friesner, R. A. ; Gullar, V. Ab initio quantum chemical and mixed quantum mechanics/molecular mechanics (QM/MM) methods for studying enzymatic catalysis. Ann. Rev. Phys. Chem. 2005, 56, 389–427.
Friesner, R. A. ; Murphy, R. B. ; Repasky, M. P. ; Frye, L. L. ; Greenwood, J. R. ; Halgren, T. A. ; Sanschagrin, P. C. ; Mainz, D. T. Extra precision GLIDE: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem. 2006, 49, 6177–6196.
Frisch, M. J. ; Trucks, G. W. ; Schlegel, H. B. ; Scuseria, G. E. ; Robb, M. A. ; Cheeseman, J. R. ; Zakrzewski, V. G. ; Montgomery, J. ; Stratmann, R. E. ; Burant, J. C. ; Dapprich, S. ; Millam, J. M. ; Daniels, A. D. ; Kudin, K. N. ; Strain, M. C. ; Farkas, O. ; Tomasi, J. ; Barone, V. ; Cossi, M. ; Cammi, R. ; Mennucci, B. ; Pomelli, C. ; Adamo, C. ; Ochterski, J. ; Petersson, G. A. ; Ayala, P. Y. ; Cui, Q. ; Morokuma, K. ; Rega, N. ; Salvador, P. ; Dannenberg, J. J. ; Malick, D. K. ; Rabuck, A. D. ; Raghavachari, K. ; Foresman, J. B. ; Cioslowski, J. ; Ortiz, J. V. ; Baboul, A. G. ; Stefanov, B. B. ; G. Liu, A. L. ; Piskorz, P. ; Komaromi, I. ; Gomperts, R. ; Martin, R. L. ; Fox, D. J. ; Keith, T. ; Al-Laham, M. A. ; Peng, C. Y. ; Nanayakkara, A. ; Challacombe, M. ; Gill, P. M. W. ; Johnson, B. ; Chen, W. ; Wong, M. W. ; Andres, J. L. ; Gonzalez, C. ; Head-Gordon, M. ; Replogle, E. S. ; Pople, J. A. ; Revision A.11.2 ed.; Gaussian, Inc.: Pittsburgh, PA, 2001.
Froloff, N. ; Windemuth, A. ; Honig, B. H. On the calculation of binding free energies using continuum methods: application to MHC class I protein-peptide interactions. Protein Sci. 1997, 6, 1293–301.
Fujitani, H. ; Tanida, Y. ; Ito, M. ; Shirts, M. R. ; Jayachandran, G. ; Snow, C. D. ; Sorin E. J. ; Pande, V. S. Direct calculation of the binding free energies of FKBP ligands. J. Chem. Phys. 2005, 123, 84–108.
Fukuzawa, K. ; Kitaura, K. ; Uebayasi, M. ; Nakata, K. ; Kaminuma, T. ; Nakano, T. Ab initio quantum mechanical study of the binding energies of human estrogen receptor alpha with its ligands: an application of fragment molecular orbital method. J. Comput. Chem. 2005, 26(1), 1–10.
Furman, R. R. ; Hoelzer, D. Purine nucleoside phosphorylase inhibition as a novel therapeutic approach for B-cell lymphoid malignancies. Semin. Oncol. 2007, 34, S29–S34.
Furneaux, R. ; Tyler, P. Improved syntheses of 3H,5H-pyrrolo[3,2-d]pyrimidines. J. Org. Chem. 1999, 64, 8411–8412.
Furse, K. E. ; Lybrand, T. P. Three-Dimensional Models for β-Adrenergic Receptor Complexes with Agonists and Antagonists. J. Med. Chem. 2003, 46, 4450.
Fusti-Molnar, L. ; Merz, K. M., Jr. An efficient and accurate molecular alignment and docking technique using ab initio quality scoring. J. Chem. Phys. 2008, 129, 25102–25113.
Güner, O. F. ; Henry, D. R. ; Pearlman, R. S. Use of flexible queries for searching conformationally flexible molecules in databases of three-dimensional structures. J. Chem. Inf. Comput. Sci. 1992, 32, 101–109.
Güner, O. F. History and evolution of the pharmacophore concept in computer-aided drug design. Curr. Top. Med. Chem. 2002, 2, 1321–1332.
Güner, O. F. Pharmacophore Perception, Development, and Use in Drug Design. La Jolla, CA: International University Line; 2000.
Galiano, L. ; Bonora, M. ; Fanucci, G. E. Interflap distances in HIV-1 protease determined by pulsed EPR measurements. J. Am. Chem. Soc. 2007, 129(36), 11004–11005.
Gallicchio, E. ; Andrec, M. ; Felts, A. K. ; Levy, R. M. Temperature weighted histogram analysis method, replica exchange, and transition paths. J. Phys. Chem. B 2005, 109, 6722–6731.
Gallicchio, E. ; Kubo, M. M. ; Levy, R. M. Enthalpy-entropy and cavity decomposition of alkane hydration free energies: Numerical results and implications for theories of hydrophobic solvation. J. Phys. Chem. B 2000, 104, 6271–6285.
Gallo, R. C. ; et al. Isolation of human T-cell leukemia-virus in acquired immune-deficiency syndrome (AIDS). Science 1983, 220(4599), 865–867.
Galmarini, C. Drug evaluation: forodesine – PNP inhibitor for the treatment of leukemia, lymphoma and solid tumor. IDrugs 2006, 9, 712–722.
Gan, W. ; Roux, B. Binding specificity of SH2 domains: insight from free energy simulations. Proteins 2008, 74, 996–1007.
Gandhi, V. ; Balakrishnan, K. Pharmacology and mechanism of action of forodesine, a T-cell targeted agent. Semin. Oncology 2007, 34, S8–S12.
Ganesan, A. The impact of natural products upon modern drug discovery. Curr. Opin. Chem. Biol. 2008, 12, 306–317.
Gao, A. M. ; Zhang, D. W. ; Zhang, J. Z. H. ; Zhang, Y. K. An efficient linear scaling method for ab initio calculation of electron density of proteins. Chem. Phys. Lett. 2004, 394(4–6), 293–297.
Garcia-Viloca, M. ; Truhlar, D. G. ; Gao, J. Importance of substrate and cofactor polarization in the active site of dihydrofolate reductase. J. Mol. Biol. 2003, 372(2), 549–560.
Garg, P. ; Verma, J. In silico prediction of blood brain barrier permeability: an artificial neural network model. J. Chem. Inf. Model. 2006, 46, 289.
Gastreich, M. ; Lilienthal, M. ; Briem, H. ; Claussen, H. Ultrafast de novo docking combining pharmacophores and combinatorics. J. Comput. Aided Mol. Des. 2006, 20, 717–734.
Geney, R. ; et al. Investigation of salt bridge stability in a generalized born solvent model. J. Chem. Theor. Comput. 2006, 2(1), 115–127.
Geney, R. ; Layten, M. ; Gomperts, R. ; Hornak, V. ; Simmerling, C. Investigation of salt bridge stability in a generalized born solvent model. J. Chem. Theory Comput. 2006, 2, 115–127.
Gerebtzoff, G. ; Seelig, A. In silico prediction of blood-brain barrier permeation using the calculated molecular cross-sectional area as main parameter. J. Chem. Inf. Model. 2006, 46, 2638.
Geschwindner, S. ; et al. Discovery of a novel warhead against beta-secretase through fragment-based lead generation. J. Med. Chem. 2007, 50, 5903–5911.
Ghanem, M. ; Saen-Oon, S. ; Zhadin, N. ; Wing, C. ; Cahill, S. ; Schwartz, S. ; Callender, R. ; Schramm, V. Tryptophan-free human PNP reveals catalytic site interactions. Biochemistry 2008, 47, 3202–3215.
Ghosh, A. K. ; Bilcer, G. ; Harwood, C. ; Kawahama, R. ; Shin, D. ; Hussain, K. A. ; Hong, L. ; Loy, J. A. ; Nguyen, C. ; Koelsch, G. ; Ermolieff, J. ; Tang, J. Structure-based design: potent inhibitors of human brain memapsin 2 (β-secretase). J. Med. Chem. 2001, 44(18), 2865–2868.
Ghosh, A. K. ; et al. Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance. J. Med. Chem. 2006, 49(17), 5252–5261.
Ghosh, A. K. ; Krishnan, K. ; Walters, D. E. ; Cho, W. ; Cho, H. ; Koo, Y. ; Trevino, J. ; Holland, L. ; Buthod, J. Structure based design: novel spirocyclic ethers as nonpeptidal P2-ligands for HIV protease inhibitors. Bioorg. Med. Chem. Lett. 1998, 8(8), 979–982.
Ghuman, J. ; Zunszain, P. A. ; Petitpas, I. ; Bhattacharya, A. A. ; Otagiri, M. ; Curry, S. Structural basis of the drug-binding specificity of human serum albumin. J. Mol. Biol. 2005, 353, 38.
Giblett, E. R. ; Ammann, A. J. ; Wara, D. W. ; Sandman, R. ; Diamond, L. K. Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet 1975, 1, 1010–1013.
Gill, A. I. ; Frederickson, M. ; Cleasby, A. ; Woodhead, S. J. ; Carr, M. G. ; Woodhead, A J. ; Walker, M. T. ; Congreve, M. S. ; et al. Identification of novel p38ct MAP kinase inhibitors using fragment-based lead generation. J. Med. Chem. 2005, 48, 414–426.
Gilson, M. K. ; Given, J. A. ; Bush, B. L. , McCammon, J. A. A statistical-thermodynamic basis for computation of binding affinities: a critical review. Biophys. J. 1997, 72(3), 1047–1069.
Gilson, M. K. ; Given, J. A. ; Bush, B. L. ; McCammon, J. A. The statistical-thermodynamic basis for computation of binding affinities: a critical review. Biophys. J. 1997, 72, 1047–1069.
Gilson, M. K. ; Honig, B. H. Calculation of the total electrostatic energy of a macromolecular system: solvation energies, binding energies, and conformational analysis. Proteins 1988, 4, 7–18.
Gilson, M. K. ; Honig, B. H. The inclusion of electrostatic hydration energies in molecular mechanics calculations. J. Comput. Aid. Mol. Des. 1991, 5, 5–20.
Gilson, M. K. ; Sharp, K. ; Honig, B. H. Calculating the electrostatic potential of molecules in solution: method and error assessment. J. Comput. Chem. 1987, 9, 327–335.
Gilson, M. K. ; Zhou, H.-X. Calculation of protein-ligand binding affinities. Annu. Rev. Biophys. Biomed. 2007, 36, 21–42.
Gilson, M. K. ; Zhou, H.-X. Calculation of protein-ligand binding affinities. Annu. Rev. Biophys. Biomol. Struct. 2007, 36, 21–42.
Gleeson, M. P. ; Waters, N. J. ; Paine, S. W. ; Davis, A. M. In silico human and rat Vss quantitative structure-activity relationship models. J. Med. Chem. 2006, 49, 1953.
Gleeson, M. P. Generation of a set of simple, interpretable ADMET rules of thumb. J. Med. Chem. 2008, 51, 817.
Gleeson, M. P. Plasma protein binding affinity and its relationship to molecular structure: an in-silico analysis. J. Med. Chem. 2007, 50, 101.
Glen, R. C. ; Allen, S. C. Ligand-protein docking: cancer research at the interface between biology and chemistry. Curr. Med. Chem. 2003, 10, 763–777.
Goeller, A. H. ; Hennemann, M. ; Keldenich, J. ; Clark, T. In silico prediction of buffer solubility based on quantum-mechanical and HQSAR- and topology-based descriptors. J. Chem. Inf. Model. 2006, 46, 648.
Gogonea, V. ; Merz, K. M., Jr. Fully quantum mechanical description of proteins in solution. combining linear scaling quantum mechanical methodologies with the Poisson-Boltzmann equation. J. Phys. Chem. A 1999, 103, 5171–5188.
Gohlke, H. ; Case, D. A. Converging free energy estimates: Mm-pb(gb)sa studies on the protein-protein complex ras-raf. J. Comput. Chem. 2004, 25, 238–250.
Golbraikh, A. ; Bonchev, D. ; Tropsha, A. Novel chirality descriptors derived from molecular topology. J. Chem. Inf. Comput. Sci. 2001, 41, 147–158.
Golbraikh, A. ; Shen, M. ; Xiao, Z. ; Xiao, Y. D. ; Lee, K. H. ; Tropsha, A. Rational selection of training and test sets for the development of validated QSAR models. J. Comput. Aided. Mol. Des. 2003a, 17, 241–253.
Golbraikh, A. ; Shen, M. ; Xiao, Z. ; Xiao, Y. D. ; Lee, K. H. ; Tropsha, A. Rational selection of training and test sets for the development of validated QSAR models. J. Comput. Aided. Mol. Des. 2003b, 17, 241–253.
Golbraikh, A. ; Tropsha, A. Beware of q2! J. Mol. Graph. Model. 2002a, 20, 269–276.
Golbraikh, A. ; Tropsha, A. Predictive QSAR modeling based on diversity sampling of experimental datasets for the training and test set selection. J. Comput. Aided Mol. Des. 2002b, 16, 357–369.
Goldberg, D. E. Genetic Algorithms in Search, Optimization and Machine Learning. Reading, MA: Addison-Wesley; 1989.
Golender, V. E. ; Vorpagel, E. R. Computer-assisted pharmacophore identification. In: 3D QSAR in Drug Design: Theory, Methods and Applications, Kubinyi, H. ; Ed. Leiden: ESCOM Science Publishers; 1993, 137–149.
Gombar, V. K. ; Polli, J. W. ; Humphreys, J. E. ; Wring, S. A. ; Serabjit-Singh, C. S. Predicting P-glycoprotein substrates by a quantitative structure-activity relationship model. J. Pharm. Sci. 2004, 93, 957.
Good, A. C. ; Kuntz, I. D. Investigating the extension of pairwise distance pharmacophore measures to triplet-based descriptors. J. Comput. Aided Mol. Des. 1995, 9, 373–379.
Gordon, C. P. ; Keller, P. A. Control of hepatitis C: a medicinal chemistry perspective. J. Med. Chem. 2005, 48, 1–20.
Gore, L. ; Stelljes, M. ; Quinones, R. Forodesine treatment and post-transplant graft-versus-host disease in two patients with acute leukemia: facilitation of graft-versus-leukemia effect? Semin. Oncol. 2007, 34, S35–39.
Goto, J. ; Kataoka, R. ; Hirayama, N. Ph4Dock: pharmacophore-based protein-ligand docking. J. Med. Chem. 2004, 47, 6804–6811.
Gouda, H. ; Kuntz, I. D. ; Case, D. A. ; Kollman, P. A. Free energy calculations for theophylline binding to an RNA aptamer: comparison of MM-PBSA and thermodynamic integration methods. Biopolymers 2003, 68, 16–34.
Gouldson, P. R. ; Kidley, N. J. ; Bywater, R. P. ; Psaroudakis, G. ; Brooks, H.D. ; Diaz, C. ; Shire, D. ; Reynolds, C.A. Toward the Active Conformations of Rhodopsin and the β2-Adrenergic Receptor. Proteins 2004, 56, 67.
Gradler, U. ; Gerber, H.-D. ; Goodenough-Lashua, D. A. M. ; Garcia, G. A. ; Ficner, R. ; Reuter, K. ; Stubbs, M. T. ; Klebe, G. A new target for shigellosis: rational design and crystallographic studies of inhibitors of tRNA-guanine transglycosylase. J. Mol. Biol. 2001, 306, 455–467.
Graham, S. L. ; Ghosh, A. K. ; Huff, J. R. ; Scholz, T. H. HIV protease inhibitors with n-terminal polyether substituents. Eur. Pat. Appl. 1993.
Gramatica P. Principles of QSAR models validation: internal and external. QSAR Comb. Sci. 2007, 26, 694–701.
Graves, A. P. ; Brenk, R. ; Shoichet, B. K. Decoys for docking. J. Med. Chem. 2005, 48, 3714–3728.
Graves, A. P. ; Shivakumar, D. M. ; Boyce, S. E. ; Jacobson, M. P. ; Case, D. A. ; Shoichet, B. K. Rescoring docking hit lists for model cavity sites: predictions and experimental. J. Mol. Biol. 2008, 377, 914–934.
Greene, J. ; Kahn, S. ; Savoj, H. ; Sprague, P. ; Teig, S. Chemical function queries for 3d database search. J. Chem. Inf. Comput. Sci. 1994, 34, 1297–1308.
Greenidge, P. A. ; Carlsson, B. ; Bladh, L. ; Gillner, M. Pharmacophores incorporating numerous excluded volumes defined by x-ray crystallographic structure in three-dimensional database searching: application to the thyroid hormone receptor. J. Med. Chem. 1998, 41, 2503–2512.
Greer, J. Comparative modeling methods: application to the family of the mammalian serine proteases. Proteins 1990, 7, 317.
Griffith, R. ; Bremner, J. B. ; Coban, B. Docking-derived pharmacophores from models of receptor-ligand complexes. In: Pharmacophore Perception, Development, and Use in Drug Design, Güner, O. F. ; Ed. La Jolla, CA: International University Line; 2000, 387–408.
Grzesiek, S. ; Bax, A. Improved 3D triple-resonance NMR techniques applied to a 31 kDa protein. J. Magn. Reson. 1992, 96, 432–440.
Guarnieri, F. Computational protein probing to identify binding sites. U.S. Patent 6735530, 2004.
Guimarães, C. R. W ; Boger, D. L. ; Jorgensen, W. L. Elucidation of fatty acid amide hydrolase inhibition by potent α-ketoheterocycle derivatives from Monte Carlo simulations. J. Am. Chem. Soc. 2005, 127, 17377–17384.
Guimaraes, C. R. W. ; Boger, D. L. ; Jorgensen, W. L. Elucidation of fatty acid amide hydrolase inhibition by potent a-ketoheterocycle derivatives from monte carlo simulations. J. Am. Chem. Soc. 2005, 127(49), 17377–17384.
Gunasekaran, K. ; Ma, B. Y. ; Nussinov, R. Is allostery an intrinsic property of all dynamic proteins? Proteins 2004, 57(3), 433–443.
Gund, P. ; Wipke, W. T. ; Langridge, R. Computer Searching of a Molecular Structure File for Pharmacophoric Patterns, Amsterdam: Elsevier; 1974, 3, 33–39.
Gund, P. Three-dimensional pharmacophore pattern searching. In: Progress in Molecular and Subcellular Biology, Hahn, F. E. ; Ed. Berlin: Springer-Verlag; 1977, 5, 117–143.
Guo, Z. ; Brooks, C. L., III , Kong, X. Efficient and flexible algorithm for free energy calculations using the λ-dynamics approach. J. Phys. Chem. B 1998, 102, 2032–2036.
Gussio, R. ; Pattabiraman, N. ; Kellogg, G. E. ; Zaharevitz, D. W. Use of 3D QSAR methodology for data mining the National Cancer Institute Repository of Small Molecules: application to HIV-1 reverse transcriptase inhibition. Methods 1998, 14, 255–263.
Héroux, A. ; White, E. ; Ross, L. ; Davis, R. ; Borhani, D. Crystal structure of Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase with XMP, pyrophosphate, and two Mg(2+) ions bound: insights into the catalytic mechanism. Biochemistry 1999, 38, 14495–14506.
Hünenberger, P. H. ; Helms, V. ; Narayana, N. ; Taylor, S. S. ; McCammon, J. A. Determinants of ligand binding to camp-dependent protein kinase. Biochemistry 1999, 38, 2358–2366.
Ha, S. ; Andreani, R. ; Robbins, A. ; Muegge, I. Evaluation of docking/scoring approaches: a comparative study based on MMP3 inhibitors. J. Comput. Aided Mol. Design 2000, 14, 435–448.
Hagemann, T. ; Robinson, S. C. ; Thompson, R. G. ; Charles, K. ; Kulbe, H. ; Balkwill, F. R. Ovarian cancer cell-derived migration inhibitory factor enhances tumor growth, progression, and angiogenesis. Mol. Cancer Ther. 2007, 6, 1993–2002.
Hajduk, P. J. ; et al. Identification of novel inhibitors of urokinase via NMR-based screening. J. Med. Chem. 2000, 43, 3862–3866.
Hajduk, P. J. ; et al. Novel inhibitors of Erm methyltransferases from NMR and parallel synthesis. J. Med. Chem. 1999, 42, 3852–3859.
Hajduk, P. J. ; Greer, J. A decade of fragment-based drug design: strategic advances and lessons learned. Nat. Rev. Drug Discov. 2007, 6, 211–219.
Hajduk, P. J. ; Huth, J. R. ; Fesik, S. W. Druggability indices for protein targets derived from NMR-based screening data. J. Med. Chem. 2005, 48(7), 2518–2525.
Hajduk, P. J. ; Huth, J. R. ; Fesik, S. W. Druggability indices for protein targets derived from NMR-based screening data. J. Med. Chem. 2005, 48, 2518–2525.
Hajduk, P. J. ; Huth, J. R. ; Sun, C. SAR by NMR: an analysis of potency gains realized through fragment-linking and fragment elaboration strategies for lead generation. In: Fragment-Based Approaches in Drug Discovery, Jahnke, W. ; Erlanson, D. A. ; Eds. Wennheim: Wiley-VCH; 2006, 181–192.
Hajduk, P. J. ; Huth, J. R. ; Tse, C. Predicting protein druggability. Drug Discov. Today 2005, 10(23–24), 1675–1682.
Hajduk, P. J. ; Meadows, R. P. ; Fesik, S. J. NMR-based screening in drug discovery. Q. Rev. Biophys. 1999, 32, 211–240.
Hajduk, P. J. ; Olejniczak, E. T. ; Fesik, S. W. One-dimensional relaxation- and diffusion-edited NMR methods for screening compounds that bind to macromolecules. J. Am. Chem. Soc. 1997, 119, 12257–12261.
Hajduk, P. J. ; Sauer, D. R. Statistical analysis of the effects of common chemical substituents on ligand potency. J. Med. Chem. 2008, 51, 553–564.
Hajduk, P. J. Fragment-based drug design: how big is too big? J. Med. Chem. 2006, 49, 6972–6976.
Hale, K. K. ; Trollinger, D. ; Rihanek, M. ; Manthey, C. L. Differential expression and activation of p38 mitogen-activated protein kinase α, β, γ and δ in inflammatory cell lineages J. Immunol. 1999, 162, 4246–4252.
Halgren, T. A . MMFF VI. MMFF94s option for energy minimization studies J. Comp. Chem. 1999, 20, 720–729.
Halgren, T. A. ; Nachbar, R. B. Merck molecular force field. IV. Conformational energies and geometries for MMFF94. J. Comp. Chem. 1996, 17, 587–615.
Halgren, T. A. ; Nachbar, R. B. Merck Molecular Force Field. IV. Conformational energies and geometries for MMFF94. J. Comput. Chem. 1996, 17, 587–615.
Halgren, T. A. Merck molecular force field. I. Basis, form, scope, parameterization and performance of MMFF94. J. Comput. Chem. 1996, 17, 520–552.
Halgren, T. A. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J. Comp. Chem. 1996, 17, 490–519.
Halgren, T. A. Merck Molecular Force Field. I. Basis, form, scope, parameterization, and performance of MMFF94. J. Comput. Chem. 1996, 17, 490–519.
Halgren, T. A. Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J. Comp. Chem. 1996, 17, 520–552.
Halgren, T. A. Merck Molecular Force Field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J. Comput. Chem. 1996, 17, 520–552.
Halgren, T. A. Merck molecular force field. III. Molecular geometries and vibrational frequencies for MMFF94. J. Comp. Chem. 1996, 17, 553–586.
Halgren, T. A. Merck Molecular Force Field. III. Molecular geometries and vibrational frequencies for MMFF94. J. Comput. Chem. 1996, 17, 553–586.
Halgren, T. A. Merck molecular force field. V. Extension of MMFF94 using experimental data, additional computational data, and empirical rules. J. Comp. Chem. 1996, 17, 616–641.
Halgren, T. A. Merck Molecular Force Field. V. Extension of MMFF94 using experimental data, additional computational data, and empirical rules. J. Comput. Chem. 1996, 17, 616–641.
Halgren, T. A. MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular-interaction energies and geometries. J. Comp. Chem. 1999, 20, 730–748.
Halperin, I. ; Ma, B. ; Wolfson, H. ; Nussinov, R. Principles of docking: an overview of search algorithms and a guide to scoring functions. Proteins 2002, 47, 409–443.
Hamelberg, D. ; McCammon, J. A. Fast peptidyl cis-trans isomerization within the flexible Gly-Rich flaps of HIV-1 protease. J. Am. Chem. Soc. 2005, 127 (40), 13778–13779.
Hamelberg, D. ; McCammon, J. A. Standard free energy of releasing a localized water molecule from the binding pockets of proteins: double-decoupling method. J. Am. Chem. Soc. 2004, 126, 7683–7689.
Hamilton, D. ; Wu, J. H. ; Batist, G. Structure-based identification of novel human γ-glutamylcysteine synthetase inhibitors. Mol. Pharm. 2007, 71, 1140–1147.
Hamming, R. Numerical Methods for Scientists and Engineers. New York: McGraw-Hill; 1962.
Hammond, G. S. A correlation of reaction rates. J. Am. Chem. Soc. 1955, 77, 334–338.
Hancock, C. N. ; Macias, A. ; Lee, E. K. ; Yu, S. Y., Jr. ; MacKerell, A. D. ; Shapiro, P. Identification of novel extracellular signal-regulated kinase docking domain inhibitors. J. Med. Chem. 2005, 48, 4586–4595.
Hann, M. M. ; Leach, A. R. ; G. Harper , G. Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Inf. Comput. Sci. 2001, 41, 856–864.
Hann, M. M. ; Leach, A. R. ; Harper, G. Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Inf. Comput. Sci. 2001, 41, 856–864.
Hann, M. M. ; Oprea, T. I. Pursuing the lead likeness concept in pharmaceutical research. Curr. Opin. Chem. Biol. 2004, 8, 255–263.
Hann, M. M. ; Oprea, T. I. Pursuing the leadlikeness concept in pharmaceutical research. Curr. Opin. Chem. Biol. 2004, 8, 255–263.
Hansch, C. ; Fujita, T. r-s-p analysis: a method for the correlation of biological activity and chemical structure. J. Am. Chem. Soc. 1964, 86, 1616–1626.
Hansch, C. ; Fukunaga, J. Designing biologically active materials. ChemTech 1977, 7(2), 120–8.
Hansch, C. ; Leo, A. Exploring QSAR: Fundamentals and Applications in Chemistry and Biology, American Chemical Society, Washington, D.C., 1995.
Hansch, C. ; Streich, M. ; Geiger, F. ; Muir, R. M. ; Maloney, P. P. ; Fujita, T. Correlation of biological activity of plant growth regulators and chloromycetin derivatives with Hammett constants and partition coefficients. J. Am. Chem. Soc. 1963, 85, 2817–2824.
Hansch, C. Quantitative approach to biochemical structure-activity relationships. Acc. Chem. Res. 1969, 2(8), 232–239.
Hanson, G. Inhibitors of p38 kinase. Expert Opin. Ther. 1997, 7, 729–733.
Hansson, T. ; Marelius, J. ; Aqvist, J. Ligand binding affinity prediction by linear interaction energy methods. J. Comput. Aided Mol. Des. 1998, 12(1), 27–35.
Hare, B. J. ; Walters, W. P. ; Caron, P. R. ; Bemis, G. W. CORES: An automated method for generating three-dimensional models of protein/ligand complexes. J. Med. Chem. 2004, 47, 4731–4740.
Harte, W. E., Jr. ; Beveridge, D. L. Prediction of the protonation state of the active site aspartyl residues in HIV-1 protease-inhibitor complexed via molecular dynamics simulation. J. Am. Chem. Soc. 1993, 115, 3883–3886.
Hartshorn, M. J. ; et al. Fragment-based lead discovery using X-ray crystallography. J. Med. Chem. 2005, 48, 403–413.
Hartshorn, M. J. ; Murray, C. W. ; Cleasby, A. ; Frederickson, M. ; Tickle, I. J. ; Jhoti, H. Fragment-based lead discovery using X-ray crystallography. J. Med. Chem. 2005, 48(2), 403–413.
Havel, T. F. ; Kuntz, I. D. ; Crippen, G. M. The theory and practice of distance geometry. Bull. Math. Biol. 1983, 45, 665–720.
Hawkins, D. M. ; Young, S. S. ; Rusinko, A. Analysis of a large structure-activity data set using recursive partitioning. Quant. Struct.-Act. Relat. 1997, 16, 1–7.
Hawkins, P. C. D. ; Skillman, A.G. ; Nicholls, A. Comparison of Shape-Matching and Docking as Virtual Screening Tools. J. Med. Chem. 2007, 50, 74.
He, X. ; Mei, Y. ; Xiang, Y. ; Zhang, D. W. ; Zhang, J. Z. H. Quantum computational analysis for drug resistance of HIV-1 reverse transcriptase to nevirapine through point mutations. Proteins 2005, 61(2), 423–432.
Head, M. S. ; Given, J. A. ; Gilson, M. K. “Mining Minima”: direct computation of conformational free energy. J. Phys. Chem. A 1997, 101, 1609–1618.
Head, M. S. ; Given, J. A. ; Gilson, M. K. Mining minima: direct computation of conformational free energy. J. Phys. Chem. A 1997, 101, 1609–1618.
Heaslet, H. ; et al. Conformational flexibility in the flap domains of ligand-free HIV protease. Acta Crystallogr. D Biol. Crystallogr. 2007, 63(Pt 8), 866–875.
Heaslet, H. ; et al. Conformational flexibility in the flap domains of ligand-free HIV protease. Acta Crystallogr. D Biol. Crystallogr. 2007, 866–875.
Hellmuth, K. ; Grosskopf, S. ; Lum, C. T. ; Wuertele, M. ; Roeder, N. ; von Kries, J. P. ; Rosario, M. ; Rademann, J. ; Birchmeier, W. Specific inhibitors of the protein tyrosine phosphatase Shp2 identified by high-throughput docking. Proc. Natl. Acad. Sci. USA 2008, 105, 7275–7280.
Helma, C. Lazy structure-activity relationships (lazar) for the prediction of rodent carcinogenicity and Salmonella mutagenicity. Mol. Divers. 2006, 10, 147–158.
Helms, V. ; Wade, R. C. Computational alchemy to calculate absolute protein-ligand binding free energy. J. Am. Chem. Soc. 1998, 120(12), 2710–2713.
Helms, V. ; Wade, R. C. Hydration energy landscape of the active site cavity in cytochrome P450cam. Proteins 1998, 32(3), 381–396.
Hendlich, M. ; Lackner, P. ; Weitckus, S. ; Floeckner, H. ; Froschauer, R. ; Gottsbacher, K. ; Casari, G. ; Sippl, M. J. Identification of native protein folds amongst a large number of incorrect models: the calculation of low energy conformations from potentials of mean force. J. Mol. Biol. 1990, 216(1), 167–180.
Hendrickson, W. A. Stereochemically restrained refinement of macromolecular structures. Methods Enzymol. 1985, 115, 252–270.
Hendrix, D. A. ; Jarzynski, C. A “fast growth” method of computing free energy differences. J. Chem. Phys. 2001, 114(14), 5974–5961.
Henin, J. ; Maigret, B. ; Tarek, M. ; Escrieut, C. ; Fourmy, D. ; Chipot, C. Probing a model of a GPCR/ligand complex in an explicit membrane environment: the human cholecystokinin-1 receptor. Biophys. J. 2006, 90(4), 1232–1240.
Henin, J. ; Maigret, B. ; Tarek, M. ; Escrieut, C. ; Fourmy, D. ; Chipot, C. Probing a Model of a GPCR/Ligand Complex in an Explicit Membrane Environment: The Human Cholecystokinin-1 Receptor. Biophys. J. 2006, 90, 1232.
Hensen, C. ; Hermann, J. C. ; Nam, K. ; Ma, S. ; Gao, J. ; Holtje, H. A combined QM/MM approach to protein-ligand interaction: polarization effects of HIV-1 protease on selected high affinity inhibitors. J. Med. Chem. 2004, 47, 6673–6680.
Hepatitis C – global prevalence (update). Weekly Epidemiology Record 1999, 74, 425–427.
Hermann, J. C. ; Hensen, C. ; Ridder, L. ; Mulholland, A. J. ; Holtje, H. D. Mechanisms of antibiotic resistance: QM/MM modeling of the acylation reaction of a class A beta-lactamase with benzylpenicillin. J. Am. Chem. Soc. 2005, 127(12), 4454–4465.
Hermann, R. B. Theory of hydrophobic bonding. II. The correlation of hydrocarbon solubility in water with solvent cavity surface area. J. Phys. Chem. 1972, 76, 2754–2759.
Hermans, J. ; Subramaniam, S. The free energy of xenon binding to myoglobin from molecular dynamics simulation. Israel J. Chem. 1986, 27, 225–227.
Hermans, J. ; Wang, L. Inclusion of the loss of translational and rotational freedom in theoretical estimates of free energies of binding. Application to a complex of benzene and mutant T4 lysozyme. J. Am. Chem. Soc. 1997, 119, 2707–2714.
Herschhorn, A. ; Hizi, A. Virtual screening, identification, and biochemical characterization of novel inhibitors of the reverse transcriptase of human immunodeficiency virus type-1. J. Med. Chem. 2008, 51, 5702–5713.
Hess, B. ; van der Vegt, N. F. A. Hydration thermodynamic properties of amino acid analogues: a comparison of biomolecular force fields and water models. J. Phys. Chem. B 2006, 110, 17616–17626.
Hibert, M. F. ; Trumpp-Kallmeyer, S. ; Bruinvels, A. ; Hofloack, J. Three-dimensional models of neurotransmitter G-binding protein-coupled receptors. Mol. Pharmacol. 1991, 40, 8.
Hibert, M. F. Protein homology modeling and drug discovery. In: The Practice of Medicinal Chemistry. New York, NY: Academic Press; 1996, 523–546.
Hirayama, K. ; Aoki, S. ; Nishikawa, K. ; Matsumoto, T. ; Wada, K. Identification of novel chemical inhibitors for ubiquitin C-terminal hydrolase-L3 by virtual screening. Bioorg. Med. Chem. 2007, 15, 6810–6818.
Hirom, P. C. ; Millburn, P. ; Smith, R. L. ; Williams, R. T. Species variations in the threshold molecular-weight factor for the biliary excretion of organic anions. Biochem. J. 1972, 129, 1071.
Hirom, P. C. ; Millburn, P. ; Smith, R. L. Bile and urine as complementary pathways for the excretion of foreign organic compounds. Xenobiotica 1976, 6, 55.
Hnizdo, V. ; Tan, J. ; Killian, B. J. ; Gilson, M. K. Efficient calculation of configurational entropy from molecular simulations by combining the mutual-information expansion and nearest-neighbor methods. J. Comput. Chem. 2008, 29(10), 1605–1614.
Hochgurtel, M. ; Lehn, J.-M. Dynamic combinatorial diversity in drug discovery. In: Fragment-Based Approaches in Drug Discovery, Vol. 34, Jahnke, W. ; Ed. Wennheim: Wiley-VCH; 2006, 341–364.
Hohwy, M. ; et al. Novel prostaglandin D synthase inhibitors generated by fragment-based drug design. J. Med. Chem. 2008, 51, 2178–2186.
Holloway, M. K. ; Wai, J. M. ; Halgren, T. A. ; Fitzgerald, P. M. D. ; Vacca, J. P. ; Dorsey, B. D. ; Levin, R. B. ; Thompson, W. J. ; Chen, J. ; deSolms, J. ; Gaffin, N. ; Ghosh, A. K. ; Giuliani, E. A. ; Graham, S. L. ; Guare, J. P. ; Hungate, R. W. ; Lyle, T. A. ; Sanders, W. M. ; Tucker, T. J. ; Wiggins, M. ; Wiscount, C. M. ; Woltersdorf, O. W. ; Young, S. D. ; Darke, P. L. ; Zugay, J. A. A priori prediction of activity for HIV-1 protease inhibitors employing energy minimization in the active site. J. Med. Chem. 1995, 38, 305–317.
Holloway, M. K. A priori prediction of ligand affinity by energy minimization. Perspectives in Drug Discovery and Design. 3D QSAR in Drug Design: Ligand/Protein Interactions and Molecular Similarity. New York: Springer-Verlag; 1998, 63–84.
Holt, D. A. ; Luengo, J. I. ; Yamashita, D. S. ; Oh, H. J. ; Konialian, A. L. ; Yen, H. K. ; Rozamus, L. W. ; Brandt, M. ; Bossard, M. J. ; Levy, M. A. ; Eggleston, D. S. ; Liang, J. ; Schultz, L. W. ; Stout, T. J. ; Clardy, J. Design, synthesis, and kinetic evaluation of high-affinity FKBP ligands and the x-ray crystal structures of their complexes with FKBP12. J. Am. Chem. Soc. 1993, 115(22), 9925–9938.
Homans, S. W. NMR spectroscopy tools for structure-aided drug design. Angew. Chem. Int. Ed. Engl. 2004, 43(3), 290–300.
Hong, L. ; Koelsch, G. ; Lin, X. ; Wu, S. ; Terzyan, S. ; Ghosh, A. K. ; Zhang, X. C. ; Tang, J. Structure of the protease domain of memapsin 2 (β-secretase) complexed with inhibitor. Science 2000, 290, 150–153.
Hong, L. ; Turner, R. T. ; Koelsch, G. ; Shin, D. ; Ghosh, A. K. ; Tang, J. Crystal structure of memapsin 2 (β-secretase) in complex with an inhibitor OM00-3. Biochemistry 2002, 41, 10963–10967.
Honig, B. H. ; Nicholls, A. Classical electrostatics in biology and chemistry. Science 1995, 268, 1144–1149.
Hoover, D. J. ; Lefkowitz-Snow, S. ; Burgess-Henry, J. L. ; Martin, W. H. ; Armento, S. J. ; Stock, I. A. ; McPherson, R. K. ; Genereux, P. E. ; Gibbs, E. M. ; Treadway, J. L. Indole-2-carboxamide inhibitors of human liver glycogen phosphorylase. J. Med. Chem. 1998, 41, 2934–2938.
Hopkins, A. L. ; Groom, C. R. ; Alex, A. Ligand efficiency: a useful metric for lead selection. Drug Discov. Today 2004, 9, 430–431.
Hopkins, S. C. ; Vale, R. D. ; Kuntz, I. D. Inhibitors of kinesin activity from structure-based computer screening. Biochemistry 2000, 39, 2805–2814.
Horenstein, B. ; Parkin, D. ; Estupiñán, B. ; Schramm, V. Transition-state analysis of nucleoside hydrolase from Crithidia fasciculata . Biochemistry 1991, 30, 10788–10795.
Hornak, V. ; Abel, R. ; Okur, A. ; Strockbine, B. ; Roitberg, A. E. ; Simmerling, C. Comparison of multiple amber force fields and development of improved protein backbone parameters. Proteins 2006, 65(3), 712–725.
Hornak, V. ; et al. HIV-1 protease flaps spontaneously close to the correct structure in simulations following manual placement of an inhibitor into the open state. J. Am. Chem. Soc. 2006, 128(9), 2812–2813.
Hornak, V. ; et al. HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations. Proc. Natl. Acad. Sci. U.S.A. 2006, 103(4), 915–920.
Hornak, V. ; et al. HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations. Proc. Natl. Acad. Sci. U.S.A. 2006, 103(4), 915–920.
Houston, J. G. ; Banks, M. N. ; Binnie, A. ; Brenner, S. ; O'Connell, J. ; Petrillo, E. W. Case study: impact of technology investment on lead discovery at Bristol Myers Squibb, 1998–2006. Drug Discov. Today 2008, 13, 44–51.
Hritz, J. ; Oostenbrink, C. Hamiltonian replica exchange molecular dynamics using soft-core interactions. J. Chem. Phys. 2008, 128(14), 144121.
Hsieh, J. H. ; Wang, X. S. ; Teotico, D. ; Golbraikh, A. ; Tropsha, A. Differentiation of AmpC beta-lactamase binders vs. decoys using classification kNN QSAR modeling and application of the QSAR classifier to virtual screening. J. Comput. Aided Mol. Des. 2008, 22(9), 593–609.
Hu, X. ; Prehna, G. ; Stebbins, C. E. Targeting plague virulence factors: a combined machine learning method and multiple conformational virtual screening for the discovery of Yersinia protein kinase A inhibitors. J. Med. Chem. 2007, 50, 3980–3983.
Huang, D. ; Lüthi, U. ; Kolb, P. ; Edler, K. ; Cecchini, M. ; Audetat, S. ; Barberis, A. ; Caflisch, A. Discovery of cell-permeable nonpeptide inhibitors of β-secretase by high-throughput docking and continuum electrostatics calculations. J. Med. Chem. 2005, 48, 5108–5111.
Huang, N. ; Jacobson, M. P. Physics-based methods for studying protein-ligand interactions. Curr. Opin. Drug Di. De. 2007, 10, 325–331.
Huang, Y. J. ; Montelione, G. T. Structural biology: proteins flex to function. Nature 2005, 438(7064), 36–37.
Hubbard, R. E. ; Davis, B. ; Chen, I. ; Drysdale, M. J. The SeeDs approach: integrating fragments into drug discovery. Curr. Top. Med. Chem. 2007, 7, 1568–1581.
Hubbell, W. L. ; Altenbach, C. ; Hubbell, C. M. ; Khorana, H.G. Rhodopsin structure, dynamics, and activation: a perspective from crystallography, site-directed spin labeling, sulfhydryl reactivity, and disulfide cross-linking. Adv. Protein Chem. 2003, 63, 243.
Hughes, B. 2007 FDA drug approvals: a year of flux. Nat. Rev. Drug Discov. 2008, 7, 107–109.
Hunt, C. ; Gillani, N. ; Farone, A. ; Rezaei, M. ; Kline, P. Kinetic isotope effects of nucleoside hydrolase from Escherichia coli . Biochim. Biophys. Acta 2005, 1751, 140–149.
Hunt, J. T. ; Mitt, T. ; Borzilleri, R. ; Gullo-Brown, J. ; Fargnoli, J. ; Fink, B. ; Han, W. -C.; Mortillo, S. ; Vite, G. ; Wautlet, B. ; Wong, T. ; Yu, C. ; Zheng, Z. ; Bhide, R. Discovery of the pyrrolo[2,1-f][1,2,4]triazine nucleus as a new kinase inhibitor template. J. Med. Chem. 2004, 47, 4054–4059.
Huo, S. ; Wang, J. ; Cieplak, P. ; Kollman, P. A. ; Kuntz, I. D. Molecular dynamics and free energy analyses of cathepsin d-inhibitor interactions: insight into structure-based ligand design. J. Med. Chem. 2002, 45, 1412–1419.
Hurst, T. Flexible 3D searching: the directed tweak technique. J. Chem. Inf. Comput. Sci. 1994, 34, 190–196.
Huskey, W. In: Enzyme Mechanism from Isotope Effects, Cook, P. F. ; Ed. Boca Raton: CRC Press; 1991, 37–72.
Huth, J. R. ; et al. Discovery and design of novel HSP90 inhibitors using multiple fragment-based design strategies. Chem. Biol. Drug Des. 2007, 70, 1–12.
Huth, J. R. ; Sun, C. Utility of NMR in lead optimization: fragment-based approaches. Comb. Chem. High Throughput Screen. 2002, 5, 631–643.
Huuskonen, J. Estimation of aqueous solubility for a diverse set of organic compounds based on molecular topology. J. Chem. Inf. Comp. Sci. 2000, 40, 773.
Hwang, Y. S. ; Chmielewski, J. Development of low molecular weight HIV-1 protease dimerization inhibitors. J. Med. Chem. 2005, 48(6), 2239–2242.
Hynes, J. , Jr.; Dyckman, A. J. ; Lin, S. ; Wrobleski, S. T. ; Wu, H. ; Gillooly, K. M. ; Kanner, S. B. ; Lonial, H. ; Loo, D. ; McIntyre, K. W. ; Pitt, S. ; Shen, D. R. ; Shuster, D. J. ; Yang, X. ; Zhang, R. ; Behnia, K. ; Zhang, H. ; Marathe, P. H. ; Doweyko, A. M. ; Tokarski, J. S. ; Sack, J. S. ; Pokross, M. ; Kiefer, S. E. ; Newitt, J. A. ; Barrish, J. C. ; Dodd, J. ; Schieven, G. L. ; Leftheris, K. Design, synthesis, and anti-inflammatory properties of orally active 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine p38α mitogen-activated protein kinase inhibitors. J. Med. Chem. 2008, 51, 4–16.
Hynes, J. ; Wu, H. ; Pitt, S. ; Shen, D. R. ; Zhang, R. ; Schieven, G. L. ; Gillooly, K. M. ; Shuster, D. J. ; Taylor, T. L. ; Yang, X. ; McIntyre, K. W. ; McKinnon, M. ; Zhang, H. ; Marathe, P. H. ; Doweyko, A. M. ; Kish, K. ; Kiefer, S. E. ; Sack, J. S. ; Newitt, J. A. ; Barrish, J. C. ; Dodd, J. ; Leftheris, K. The discovery of (R)-2-(sec-butylamino)-N-(2-methyl-5-(methyl-carbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994) – A potent and efficacious p38α MAP kinase inhibitor. Bioorg. Med. Chem. Lett. 2008, 18, 1762–1767.
ICM-Pro 2.8 docking module. San-Diego: Molsoft LLC.
Identification of BRAF inhibitors through in silico screening. J. Med. Chem. 2008, 51, 6121–6127.
Iino, M. ; Furugori, T. ; Mori, T. ; Moriyama, S. ; Fukuzawa, A. ; Shibano, T. Rational design and evaluation of new lead compound structures for selective βARK1 inhibitors. J. Med. Chem. 2002, 45, 2150–2159.
Ikura, M. ; Kay, L.E. ; Bax, A. A novel approach for sequential assignment of 1H, 13C, and 15N spectra of proteins: heteronuclear triple-resonance three-dimensional NMR spectroscopy. Application to calmodulin. Biochemistry 1990, 29, 4659–4667.
Im, W. ; Feig, M. ; Brooks, C. L. An Implicit Membrane Generalized Born Theory for the Study of Structure, Stability, and Interactions of Membrane Proteins. Biophys. J. 2003, 85, 2900.
In Management of Hepatitis C: 2002; National Institutes of Health, 2002. http://consensus.nih.gov/2002/2002HepatitisC2002116html.htm.
Irving, J. A. ; Whisstock, J. C. ; Lesk, A. M. Protein structural alignments and functional genomics. Proteins 2001, 42, 378–382.
Irwin, J. J. ; Raushel, F. M. ; Shoichet, B. K. Virtual screening against metalloenzymes for inhibitors and substrates. Biochemistry 2005, 44(37), 12316–12328.
Irwin, J. J. ; Raushel, F. M. ; Shoichet, B. K. Virtual screening against metalloenzymes for inhibitors and substrates. Biochemistry 2005, 44, 12316–12328.
Irwin, J. J. ; Shoichet, B. K. ZINC – a free database of commercially available compounds for virtual screening. J. Chem. Inf. Model. 2005, 45, 177–182.
Irwin, J. J. ; Shoichet, B. K. ZINC: a free database of commercially available compounds for virtual screening. J. Chem. Inf. Model. 2005, 45(1), 177–182.
Irwin, J. J. ; Shoichet, B. K. ZINC: a free database of commercially available compounds for virtual screening. J. Chem. Inf. Model. 2005, 45, 177–182.
Irwin, J. J. Shoichet, B. K. ZINC – a free database of commercially available compounds for virtual screening. J. Chem. Inf. Model. 2005, 45, 177–182.
Ishima, R. ; et al. Flap opening and dimer-interface flexibility in the free and inhibitor-bound HIV protease, and their implications for function. Structure 1999, 7(9), 1047–1055.
Ishima, R. ; Louis, J. M. A diverse view of protein dynamics from NMR studies of HIV-1 protease flaps. Proteins 2007, 70, 1408–1415.
Iwadate, M. ; Asakura, T. ; Williamson, M. P. C-alpha and C-beta carbon-13 chemical shifts in proteins from an empirical database. J. Biomol. NMR 1999, 13(3), 199–211.
Iwata, Y. ; Arisawa, M. ; Hamada, R. ; Kita, Y. ; Mizutani, M. Y. ; Tomioka, N. ; Itai, A. ; Miyamoto, S. Discovery of novel aldose reductase inhibitors using a protein structure-based approach: 3D-database search followed by design and synthesis. J. Med. Chem. 2001, 44, 1718–1728.
Jack, A. ; Levitt, M. Refinement of large structures by simultaneous minimization of energy and R factor. Acta Crystallogr. A 1978, 34, 931–935.
Jackson, P. F. ; Bullington, J. L. Pyridinylimidazole based p38 MAP kinase inhibitors. Curr. Top. Med. Chem. 2002, 2, 1011–1020.
Jacobsson, M. ; Gäredal, M. ; Schultz, J. ; Karlén, A. Identification of plasmodium falciparum spermidine synthase active site binders through structure-based virtual screening. J. Med. Chem. 2008, 51, 2777–2786.
Jacoby, E. ; Davies, J. ; Blommers, M. J. Design of small molecule libraries for NMR screening and other applications in drug discovery. Curr. Top. Med. Chem. 2003, 3, 11–23.
Jahnke, W. ; et al. Second-site NMR screening with a spin-labeled first ligand. J. Am. Chem. Soc. 2000, 122, 7394–7395.
Jahnke, W. ; Rudisser, S. ; Zurini, M. Spin label enhanced NMR screening. J. Am. Chem. Soc. 2001, 123, 3149–3150.
Jakalian, A. ; Bush, B. L. ; Jack, D. B. ; Bayly, C. I. Fast, efficient generation of high-quality atomic charges, AM1-BCC model. I. Method. J. Comput. Chem. 2000, 21(2), 132–146.
Jakalian, A. ; Jack, D. B. ; Bayly, C. I. Fast, efficient generation of high-quality atomic charges, AM1-BCC model. II. Parameterization and validation. J. Comput. Chem. 2002, 23(16), 1623–1641.
Jakobsen, P. ; Lundbeck, J. M. ; Kristiansen, M. ; Breinholt, J. ; Demuth, H. ; Pawlas, J. ; Torres Candela, M. P. ; Anderson, B. ; Westergaard, N. ; Lundgren, K. ; Asano N. Iminosugars: potential inhibitors of liver glycogen phosphorylase. Bioorg. Med. Chem. 2001, 9, 733–744.
Jancarik, J. ; Kim, S.-H. Sparse matrix sampling: a screening method for crystallization of proteins. J. Appl. Crystallogr. 1991, 24, 409–411.
Jarzynski, C. Rare events and the convergence of exponentially averaged work values. Phys. Rev. E 2006, 73, 046105.
Jayachandran, G. ; Shirts, M. R. ; Park, S. ; Pande, V. S. Parallelized-over-parts computation of absolute binding free energy with docking and molecular dynamics. J. Chem. Phys. 2006, 125, 084901.
Jencks, W. Binding energy, specificity, and enzymic catalysis: the Circe effect. Adv. Enzymol. Relat. Areas Mol. Biol. 1975, 43, 219–410.
Jencks, W. In: Catalysis in Chemistry and Enzymology. Dover: New York, 1987, 170–182.
Jencks, W. P. On the attribution and additivity of binding energies. Proc. Natl. Acad. Sci. U.S.A. 1981, 78, 4046–4050.
Jian Shen, J. W. Electrostatic binding energy calculation using the finite difference solution to the linearized Poisson-Boltzmann equation: assessment of its accuracy. J. Comput. Chem. 1996, 17, 350–357.
Jiang, Y. ; Ichikawa, Y. ; Stivers, J. Inhibition of uracil DNA glycosylase by an oxacarbenium ion mimic. Biochemistry 2002, 41, 7116–7124.
Jiang, Y. ; Lee, A. ; Chen, J. ; Cadene, M. ; Chait, B. T. ; MacKinnon, R. The open pore conformation of potassium channels. Nature 2002, 417(6888), 523–526.
Jiang, Y. ; Lee, A. ; Chen, J. ; Ruta, V. ; Cadene, M. ; Chait, B. T. ; MacKinnon, R. X-ray structure of a voltage-dependent K+ channel. Nature 2003, 423(6935), 33–41.
Jiao, D. ; Golubkov, P. A. ; Darden, T. A. ; Ren, P. Calculation of protein-ligand binding free energy using a polarizable potential. Proc. Natl. Acad. Sci. U.S.A. 2008, 105(17), 6290–6295.
Johnson, E. C. ; Feher, V. A. ; Peng, J. W. ; Moore, J. M. ; Williamson, J. R. Application of NMR SHAPES screening to an RNA target. J. Am. Chem. Soc. 2003, 125, 15724–15725.
Johnson, L. N. Glycogen phosphorylase: control by phosphorylation and allosteric effectors. FASEB J. 1992, 6, 2274–2282.
Johnson, S. R. ; Chen, X. Q. ; Murphy, D. ; Gudmundsson, O. A. Computational model for the prediction of aqueous solubility that includes crystal packing, intrinsic solubility, and ionization effects. Mol. Pharm. 2007, 4, 513.
Johnson, S. R. ; Zheng, W. Recent progress in the computational prediction of aqueous solubility and absorption. AAPS J. 2006, 8, E27.
Johnson, S. R. The trouble with QSAR (or how I learned to stop worrying and embrace fallacy). J. Chem. Inf. Model. 2008, 48, 25–26.
Jones, G. ; Willett, P. ; Glen, R. C. A genetic algorithm for flexible molecular overlay and pharmacophore elucidation. J. Comput. Aided Mol. Des. 1995, 9, 532–549.
Jones, R. ; Connolly, P. C. ; Klamt, A. ; Diedenhofen, M. Use of surface charges from DFT calculations to predict intestinal absorption. J. Chem. Inf. Model. 2005, 45, 1337.
Jorgensen, W. L. ; Duffy, E. M. Prediction of solubility from structure. Adv. Drug Deliv. Rev., 54, 355–365.
Jorgensen, W. L. ; Maxwell, D. S. ; Tirado-Rives, J. Development and testing of the opls all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 1996, 118, 11225–11236.
Jorgensen, W. L. ; Ravimohan, C. Monte Carlo simulation of differences in free energies of hydration. J. Chem. Phys. 1985, 83(6), 3050–3054.
Jorgensen, W. L. ; Ravimohan, C. Monte Carlo simulation of differences in free energies of hydration. J. Chem. Phys. 1985, 83, 3050–3054.
Jorgensen, W. L. ; Ruiz-Caro, J. ; Tirado-Rives, J. ; Basavapathruni, A. ; Anderson, K. S. ; Hamilton, A. D. Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett. 2006, 16(3), 663–667.
Jorgensen, W. L. ; Ruiz-Caro, J. ; Tirado-Rives, J. ; Basavapathruni, A. ; Anderson, K. S. ; Hamilton, A. D. Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett. 2006, 16, 663–667.
Jorgensen, W. L. ; Thomas, L. T. Perspective on free-energy perturbation calculations for chemical equilibria. J. Chem. Theor. Comput. 2008, 4, 869–876.
Jorgensen, W. L. ; Tirado-Rives, J. Molecular modeling of organic and biomolecular systems using BOSS and MCPRO. J. Comput. Chem. 2005, 26, 1689–1700.
Jorgensen, W. L. ; Tirado-Rives, J. Potential energy functions for atomic-level simulations of water and organic and biomolecular systems. Proc. Nat. Acad. Sci U.S.A. 2005, 102, 6665–6670.
Jorgensen, W. L. ; Tirado-Rives, J. QSAR/QSPR and proprietary data. J. Chem. Inf. Model. 2006, 46, 937.
Jorgensen, W. L. ; Tirado-Rives, J. The OPLS (optimized potentials for liquid simulations) potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. J. Am. Chem. Soc. 1988, 110(6), 1657–66.
Jorgensen, W. L. Free energy calculations: a breakthrough for modeling organic chemistry in solution. Accounts Chem. Res. 1989, 22(5), 184–189.
Jorgensen, W. L. QIKPROP, v 3.0. New York: Schrödinger LLC; 2006.
Jorgensen, W. L. The many roles of computation in drug discovery. Science 2004, 303(5665), 1813–1818.
Jorgensen, W. L. The many roles of computation in drug discovery. Science 2004, 303(5665), 1813–1818.
Jorgensen, W. L. The many roles of computation in drug discovery. Science 2004, 303, 1813–1818.
Kaminski, G. ; Friesner, R. A. ; Rives, J. ; Jorgensen, W. L. Evaluation and reparametrization of the opls-aa force field for proteins via comparison with accurate quantum chemical calculations on peptides. J. Phys. Chem. B 2001, 105(28), 6474–6487.
Kamionka, M. ; Rehm, T. ; Beisel, H.-G. ; Lang, K. ; Engh, R. A. ; Holak, T. A. In silico and NMR identification of inhibitors of the IGF-I and IGF-Binding Protein-5 interaction. J. Med. Chem. 2002, 45, 5655–5660.
Kangas, E. ; Tidor, B. Optimizing electrostatic affinity in ligand-receptor binding: theory, computation, and ligand properties. J. Chem. Phys. 1998, 109(17), 7522–7545.
Kanji., G. K. 100 Statistical Tests, 3rd edition. Thousand Oaks, CA: Sage, 2006.
Karelson, M. ; Lobanov, V. S. ; Katritzky, A. R. Quantum-chemical descriptors in QSAR/QSPR studies. Chem. Rev. 1996, 96(3), 1027–1044.
Karplus, M. Molecular dynamics of biological macromolecules: a brief history and perspective. Biopolymers 2003, 68(3), 350–358.
Katoh, E. ; et al. A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex. Protein Sci. 2003, 12(7), 1376–1385.
Katritch, V. ; Byrd, C. M. ; Tseitin, V. ; Dai, D. ; Raush, E. ; Totrov, M. ; Abagyan, R. ; Jordan, R. ; Hruby, D. E. Discovery of small molecule inhibitors of ubiquitin-like poxvirus proteinase I7L using homology modeling and covalent docking approaches. J. Comput. Aided Mol. Des. 2007, 21, 549–558.
Kelder, J. ; Grootenhuis, P. D. ; J. Bayada, D. M. ; Delbressine, L. P. C. ; Ploemen, J. P. Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs. Pharm. Res. 1999, 16, 1514.
Kellenberger, E. ; Rodrigo, J. ; Muller, P. ; Rognan, D. Comparative evaluation of eight docking tools for docking and virtual screening accuracy. Proteins 2004, 57, 225–242.
Kellenberger, E. ; Springael, J. Y. ; Parmentier, M. ; Hachet-Haas, M. ; Galzi, J. L. ; Rognan, D. Identification of Nonpeptide CCR5 Receptor Agonists by Structure-based Virtual Screening. J. Med. Chem. 2007, 50, 1294.
Keseru, G. M. ; Makara, G. M. Hit discovery and hit-to-lead approaches. Drug Discov. Today 2006, 11, 741–748.
Khandelwal, A. ; Lukacova, V. ; Comez, D. ; Kroll, D. M. ; Raha, S. ; Balaz, S. A combination of docking, QM/MM methods, and MD simulation for binding affinity estimation of metalloprotein ligands. J. Med. Chem. 2005, 48(17), 5437–5447.
Khandogin, J. ; Musier-Forsyth, K. ; York, D. M. Insights into the regioselectivity and RNA-binding affinity of HIV-1 nucleocapsid protein from linear-scaling quantum methods. J. Mol. Biol, 2003, 330, 993–1004.
Khandogin, J. ; York, D. M. Quantum descriptors for biological macromolecules from linear-scaling electronic structure methods. Proteins 2004, 56, 724–737.
Khoruzhii, O. ; Donchev, A. G. ; Galkin, N. ; Illarionov, A. ; Olevanov, M. ; Ozrin, V. ; Queen, C. ; Tarasov, V. Application of a polarizable force field to calculations of relative protein-ligand binding affinities. Proc. Natl. Acad. Sci. U.S.A. 2008, 105(30), 10378–10383.
Kicska, G. ; Long, L. ; Hörig, H. ; Fairchild, C. ; Tyler, P. ; Furneaux, R. ; Schramm, V. ; Kaufman, H. Immucillin H, a powerful transition-state analog inhibitor of purine nucleoside phosphorylase, selectively inhibits human T lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 4593–4598.
Kicska, G. A. ; Tyler, P. C. ; Evans, G. B. ; Furneaux, R. H. ; Kim, K. ; Schramm, V. L. Transition state analogue inhibitors of purine nucleoside phosphorylase from Plasmodium falciparum . J. Biol. Chem. 2002, 277, 3219–3225.
Kicska, G. A. ; Tyler, P. C. ; Evans, G. B. ; Furneaux, R. H. ; Shi, W. X. ; Fedorov, A. ; Lewandowicz, A. ; Cahill, S. M. ; Almo, S. C. ; Schramm, V. L. Atomic dissection of the hydrogen bond network for transition-state analogue binding to purine nucleoside phosphorylase. Biochemistry 2002, 41, 14489–14498.
Killian, B. J. ; Yundenfreund Kravitz, J. ; Gilson, M. K. Extraction of configurational entropy from molecular simulations via an expansion approximation. J. Chem. Phys. 2007, 127(2), 024107.
Kim, B. ; Cha, S. ; Parks, R. J. Purine nucleoside phosphorylase from human erythroyctes. II. Kinetic analysis and substrate-binding studies. J. Biol. Chem. 1968, 243, 1771–1776.
Kim, J. T. ; Hamilton, A. D. ; Bailey, C. M. ; Domaoal, R. A. ; Wang, L. ; Anderson, K. S. ; Jorgensen, W. L. FEP-guided selection of bicyclic heterocycles in lead optimization for non-nucleoside inhibitors of HIV-1 reverse transcriptase. J. Am. Chem. Soc. 2006, 128, 15372–15373.
Kim, J. T. ; Hamilton, A. D. ; Bailey, C. M. ; Domoal, R. A. ; Wang, L. ; Anderson, K. S. ; Jorgensen, W. L. Fep-guided selection of bicyclic heterocycles in lead optimization for non-nucleoside inhibitors of HIV-1 reverse transcriptase. J. Am. Chem. Soc. 2006, 128(48), 15372–15373.
Kim, R. ; Skolnick, J. Assessment of programs for ligand binding affinity prediction. J. Comp. Chem. 2008, 29, 1316–1331.
Kimble, E. ; Hadala, J. ; Ludewig, R. ; Peters, P. ; Greenberg, G. ; Xiao, G. ; Guida, W. ; McQuire, L. ; Simon, P. The biochemical and pharmacological activity of 9-benzyl-9-deazaguanine, a potent purine nucleoside phosphorylase (PNP) inhibitor. Inflamm. Res. 1995, 44(suppl. 2), S181–S182.
Kirchhoff, P. D. ; Brown, R. ; Kahn, S. ; Waldman, M. Application of structure-based focusing to the estrogen receptor. J. Comput. Chem. 2001, 22, 993–1003.
Kiss, R. ; Kiss, B. ; Könczöl, A. ; Szalai, F. ; Jelinek, I. ; László, V. ; Noszál, B. ; Falus, A. ; Keserũ, G. M. Discovery of Novel Human Histamine H4 Receptor Ligands by Large-Scale Structure-Based Virtual Screening. J. Med. Chem. 2008, 51, 3145.
Kiss, R. ; Koᾓri, Z. ; Keserũ, G. M. Homology modeling and binding site mapping of the human histamine H1 receptor Eur. J. Med. Chem. 2004, 39, 959.
Kitchen, D. B. ; Decornez, H. ; Furr, J. R. ; Bajorath, J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat. Rev. Drug Discov. 2004, 3, 935–949.
Kjellander, B. ; Masimirembwa, C. M. ; Zamora, I. Exploration of enzyme-ligand interactions in CYP2D6 & 3A4 homology models and crystal structures using a novel computational approach. J. Chem. Inf. Model. 2007, 47, 1234.
Klahn, M. ; Braun-Sand, S. ; Rosta, E. ; Warshel, A. On possible pitfalls of ab initio quantum mechanics/molecular mechanics minimization approaches for studies of enzymatic reactions. J. Phys. Chem. B 2005, 109, 15645–15650.
Klaus, W. ; Senn, H. Strategies for hit finding using NMR. In: BioNMR in Drug Research, Zerbe, O. ; Ed. Weinheim: Wiley-VCH; 2003, 417–437.
Klebe, G. ; Abraham, U. ; Mietzner, T. Molecular similarity indices in comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J. Med. Chem. 1994, 37, 4130–4146.
Klebe, G. Comparative molecular similarity indices: CoMSIA. In: 3D QSAR in Drug Design, Vol. 3, Kubinyi, H. ; Folkers, G. ; Martin, Y. C. ; Eds. London: Kluwer Academic; 1998, 87.
Kleywegt, G. J. ; Henrick, K. ; Dodson, E. J. ; Van Aalten, D. M. F. Pound-wise but penny-foolish: how well do micromolecules fare in macromolecular refinement? Structure 2003, 11(9), 1051–1059.
Kleywegt, G. J. ; Jones, A. T. Where freedom is given, liberties are taken. Structure 1995, 3, 535–540.
Kleywegt, G. J. ; Jones, T. A. Databases in protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 1998, 54, 1119–1131.
Kleywegt, G. J. ; Jones, T. A. Where freedom is given, liberties are taken. Structure 1995, 3(6), 535–540.
Kleywegt, G. J. Crystallographic refinement of ligand complexes. Acta Crystallogr. D Biol. Crystallogr. 2007, D63(1), 94–100.
Kline, P. ; Schramm, V. Pre-steady-state transition-state analysis of the hydrolytic reaction catalyzed by purine nucleoside phosphorylase. Biochemistry 1995, 34, 1153–1162.
Kline, P. ; Schramm, V. Purine nucleoside phosphorylase: catalytic mechanism and transition-state analysis of the arsenolysis reaction. Biochemistry 1993, 32, 13212–13219.
Kline, P. ; Schramm, V. Purine nucleoside phosphorylase: inosine hydrolysis, tight binding of the hypoxanthine intermediate, and third-the-sites reactivity. Biochemistry 1992, 31, 5964–5973.
Knox, A. J. S. ; Meegan, M. J. ; Sobolev, V. ; Frost, D. ; Zisterer, D. M. ; Williams, D. C. ; Lloyd, D. G. Target specific virtual screening: optimization of an estrogen receptor screening platform. J. Med. Chem. 2007, 50, 5301–5310.
Kobilka, B. ; Schertler, F. X. New G-protein-coupled receptor crystal structures: insights and limitations. Trends Pharmacol. Sci. 2008, 29, 79.
Kohen, A. ; Cannio, R. ; Bartolucci, S. ; Klinman, J. Enzyme dynamics and hydrogen tunnelling in a thermophilic alcohol dehydrogenase. Nature 1999, 399, 496–499.
Kohl, N. E. ; et al. Active human immunodeficiency virus protease is required for viral infectivity. Proc. Natl. Acad. Sci. U.S.A. 1988, 85(13), 4686–4690.
Kola, I. ; Landis, J. Opinion: Can the pharmaceutical industry reduce attrition rates? Nature Rev. Drug Disc. 2004, 3, 711.
Kolb, P. ; Huang, D. ; Dey, F. ; Caflisch, A. Discovery of kinase inhibitors by high-throughput docking and scoring based on a transferable linear interaction energy model. J. Med. Chem. 2008, 51, 1179–1188.
Kollman, P. A. ; Massova, I. ; Reyes, C. ; Kuhn, B. ; Huo, S. ; Chong, L. ; Lee, M. ; Lee, T. ; Duan, Y. ; Wang, W. ; Donini, O. ; Cieplak, P. ; Srinivasan, J. ; Case, D. A. ; Cheatham, T. E. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc. Chem. Res. 2000, 33, 889–897.
Kollman, P. A. Free energy calculations: applications to chemical and biochemical phenomena. Chem. Rev. 1993, 7, 2395–2417.
Kollman, P. A. Free energy calculations: applications to chemical and biochemical phenomena. Chem. Rev. 1993, 93, 2395–2417.
Kolossváry, I. Evaluation of the molecular configuration integral in all degrees of freedom for the direct calculation of conformational free energies: prediction of the anomeric free energy of monosaccharides. J. Phys. Chem. A 1997, 101(51), 9900–9905.
Kolossváry, I. Evaluation of the molecular configuration integral in all degrees of freedom for the direct calculation of conformational free energies: prediction of the anomeric free energy of monosaccharides. J. Phys. Chem. A 1997, 101(51), 9900–9905.
Kolykhalov, A. A. ; Mihalik, K. ; Feinstone, S. M. ; Rice, C. M. Hepatitis C virus-encoded enzymatic activities and conserved RNA elements in the 3' nontranslated region are essential for virus replication in vivo. J. Virol. 2000, 74, 2046–2051.
Kong, X. ; Brooks, C. L., III . λ-dynamics: a new approach to free energy calculations. J. Chem. Phys. 1996, 105(6), 2414–2423.
Kontoyianni, M. ; DeWeese, C. ; Penzotti, J. E. ; Lybrand, T. P. Three-Dimensional Models for Agonist and Antagonist Complexes with β2 Agrenergic Receptor. J. Med. Chem. 1996, 4406.
Kontoyianni, M. ; Madhav, P. ; Suchanek, E. ; Seibel, W. Theoretical and practical considerations in virtual screening: a beaten field? Curr. Med. Chem. 2008, 15, 107–116.
Koppitz, M. ; Eis, K. Automated medicinal chemistry. Drug Discov. Today 2006, 11, 561–568.
Korycka, A. ; Blonski, J. Z. ; Robak, T. Forodesine (BCX-1777, Immucillin H) – a new purine nucleoside analogue: mechanism of action and potential clinical application. Mini Rev. Med. Chem. 2007, 7, 976–983.
Kovatcheva, A. ; Buchbauer, G. ; Golbraikh, A. ; Wolschann, P. QSAR modeling of alpha-campholenic derivatives with sandalwood odor. J. Chem. Inf. Comput. Sci. 2003, 43, 259–266.
Kovatcheva, A. ; Golbraikh, A. ; Oloff, S. ; Xiao, Y. D. ; Zheng, W. ; Wolschann, P. ; Buchbauer, G. ; Tropsha, A. Combinatorial QSAR of ambergris fragrance compounds. J. Chem. Inf. Comput. Sci. 2004, 44, 582–595.
Kratochwil, N. A. ; Huber, W. ; Mueller, F. ; Kansy, M. ; Gerber, P. R. Predicting plasma protein binding of drugs – revisited. Curr. Opin. Drug Disc. Devel. 2004, 7, 507.
Kratochwil, N. A. ; Huber, W. ; Muller, F. ; Kansy, M. ; Gerber, P. R. Predicting plasma protein binding of drugs: a new approach. Biochem. Pharmacol. 2002, 64, 1355.
Krausslich, H. G. Human immunodeficiency virus proteinase dimer as component of the viral polyprotein prevents particle assembly and viral infectivity. Proc. Natl. Acad. Sci. U.S.A. 1991, 88(8), 3213–3217.
Krenitsky, T. Purine nucleoside phosphorylase: kinetics, mechanism, and specificity. Mol. Pharmacol. 1967, 3, 526–536.
Kristiansen, M. ; Anderson, B. ; Iversen, L. F. ; Westergaard, N. Identification, synthesis, and characterization of new glycogen phosphorylase inhibitors binding to the allosteric AMP site. J. Med. Chem. 2004, 47, 3537–3545.
Kroeger Smith, M. B. ; Rader, L. H. ; Franklin, A. M. ; Taylor, E. V. ; Smith, K. D. ; Tirado-Rives, J. ; Jorgensen, W. L. Energetic effects for observed and unobserved HIV-1 reverse transcriptase mutations of residues l100, v106, and y181 in the presence of nevirapine and efavirenz. Bioorg. Med. Chem. Lett. 2008, 18(3), 969–972.
Kubinyi, H. ; Hamprecht, F. A. ; Mietzner, T. Three-dimensional quantitative similarity-activity relationships (3D QSiAR) from SEAL similarity matrices. J. Med. Chem. 1998, 41, 2553–2564.
Kuhn, B. ; Donini, O. ; Huo, S. ; Wang, J. ; Kollman, P. A. MM-PBSA applied to computer-assisted ligand design. In: Free Energy Calculations in Rational Drug Design, Rami Reddy, R. ; Erion, M. D. ; Eds. New York: Kluwer Academic/Plenum; 2001, 243–251.
Kuhn, B. ; Gerber, P. R. ; Schulz-Gasch, T. ; Stahl, M. Validation and use of the MM-PBSA approach for drug discovery. J. Med. Chem. 2005, 48, 4040–4048.
Kuhn, B. ; Kollman, P. A. ; Stahl, M. Prediction of pka shifts in proteins using a combination of molecular mechanical and continuum solvent calculations. J. Comput. Chem. 2004, 25, 1865–1872.
Kuhn, B. ; Kollman, P. A. A ligand that is predicted to bind better to avidin than biotin: insights from computational fluorine scanning. J. Am. Chem. Soc. 2000, 122, 3909–3916.
Kuhn, B. ; Kollman, P. A. Binding of a diverse set of ligands to avidin and streptavidin: an accurate quantitative prediction of their relative affinities by a combination of molecular mechanics and continuum solvent models. J. Med. Chem. 2000, 43, 3786–3791.
Kumar, S. ; Bouzida, D. ; Swendsen, R. H. ; Kollman, P. A. ; Rosenberg, J. M. The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method. J. Comput. Chem. 1992, 13(8), 1011–1021.
Kuntz, I. D. ; Meng; E. C. ; Shoichet, B. K. Structure-based molecular design. Acc. Chem. Res. 1994, 27, 117–123.
Kuntz, I. D. Structure-based strategies for drug design and discovery. Science 1992, 257, 1078–1082.
Kuo, C.-J. ; Guo, R.-T. ; Lu, I.-L. ; Liu, H. G. ; Wu, S.-Y. ; Ko, T.-P. ; Wang, A. H.-J. ; Liang, P.-H. Structure-based inhibitors exhibit differential activities against Helicobacter pylori and Escherichia coli undecaprenyl pyrophosphate synthases. J. Biomed. Biotechnol. 2008.
Kuszewski, J. ; Nilges, M. ; Brunger, A. T. Sampling and efficiency of metric matrix distance geometry: a novel partial metrization algorithm. J. Biomol. NMR 1992, 2, 33–56.
Kuzuyama, T. ; Noel, J. P. ; Richard, S. B. Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products. Nature 2005, 435(7044), 983–987.
Lahana, R. How many leads from HTS? Drug Discov. Today 1999, 4, 447–448.
Lajiness, M. S. Dissimilarity-based compound selection techniques. Perspect. Drug Discov. Des. 1997, 7/8, 65–84.
Lamanna, C. ; Bellini, M. ; Padova, A. ; Westerberg, G. ; Maccari, L. Straightforward recursive partitioning model for discarding insoluble compounds in the drug discovery process. J. Med. Chem. 2008, 51, 2891.
Lamb, M. L. ; Tirado-Rives, J. ; Jorgensen, W. L. Estimation of the binding affinities of FKBP12 inhibitors using a linear response method. Bioorg. Med. Chem. 1999, 7(5), 851–860.
Landon, M. R. ; Lancia, D. R., Jr. ; Yu, J. ; Thiel, S. C. ; Vajda, S. Identification of hot spots within druggable binding regions by computational solvent mapping of proteins. J. Med. Chem. 2007, 50, 1231–1240.
Lange, O. F. ; Lakomek, N.-A. ; Farès, C. ; Schröder, G. F. ; Walter, K. F. A. ; Becker, S. ; Meiler, J. ; Grubmüller, H. ; Griesinger, C. ; de Groot, B. L. Recognition dynamics up to microseconds revealed from an RDC-derived ubiquitin ensemble in solution. Protein, 2008, 320(5882) 1471–1475.
LangeSavage, G. ; et al. Structure of HOE/BAY 793 complexed to human immunodeficiency virus (HIV-1) protease in two different crystal forms – structure/function relationship and influence of crystal packing. Eur. J. Biochem. 1997, 248(2), 313–322.
Lanyi, J. ; Luecke, H. Bacteriorhodopsin. Curr. Opin. Struc. Biol. 2001, 11, 415.
Lanyi, J. K. Bacteriorhodopsin. Annu. Rev. Physiol. 2004, 66 665.
Lapatto, R. ; et al. X-ray analysis of HIV-1 proteinase at 2.7 [angst] resolution confirms structural homology among retroviral enzymes. Nature 1989, 342(6247), 299–302.
Lapatto, R. ; et al. X-ray-analysis of HIV-1 proteinase at 2.7 a resolution confirms structural homology among retroviral enzymes. Nature 1989, 342(6247), 299–302.
Laplante, R. ; Llinas-Brunet, M. Dynamics and Structure-based Design of Drugs Targeting the Critical Serine Protease of the Hepatitis C Virus – From a Peptidic Substrate to BILN 2061. Curr. Med. Chem. Antinfect. Agents 2005, 4, 111–132.
Larson, R. A. Three new drugs for acute lymphoblastic leukemia: nelarabine, clofarabine, and forodesine. Semin. Oncol. 2007, 34, S13–20.
Lauri, G. ; Bartlett, P. A. CAVEAT: a program to facilitate the design of organic molecules. J. Comput. Aided Mol. Des. 1994, 8, 51–66.
Layten, M. ; Hornak, V. ; Simmerling, C. The open structure of a multi-drug-resistant HIV-1 protease is stabilized by crystal packing contacts. J. Am. Chem. Soc. 2006, 128(41), 13360–13361.
Layten, M. ; Hornak, V. ; Simmerling, C. The open structure of a multi-drug-resistant HIV-1 protease is stabilized by crystal packing contacts. J. Am. Chem. Soc. 2006, 128(41), 13360–13361.
Lazaridis, T. ; Karplus, M. Effective energy functions for protein structure prediction. Curr. Opin. Struct. Biol. 2000, 10(2), 139–145.
Leach, A. G. ; Jones, H. D. ; Cosgrove, D. A. ; Kenny, P. W. ; Ruston, L. ; MacFaul, P. ; Wood, J. M. ; Colclough, N. ; Law, B. Matched molecular pairs as a guide in the optimization of pharmaceutical properties; a study of aqueous solubility, plasma protein binding and oral exposure. J. Med. Chem. 2006, 49, 6672.
Leach, A. R. ; Hann, M. M. ; Burrows, J. N. ; Griffen, E. J. Fragment screening: an introduction. Mol. Biosyst. 2006, 2, 429–446.
Leach, A. R. ; Shoichet, B. K. ; Peishoff, C. E. Prediction of protein-ligand interactions. Docking and scoring: successes and gaps. J. Med. Chem. 2006, 49, 5851–5855.
Leach, A. R. Molecular Modeling Principles and Applications. Essex, UK: Prentice Hall; 2001.
Leach, A. R. Molecular Modelling: Principles and Applications. Harlow, Essex, England: Addison Wesley Longman Limited; 1996.
Lee, J. C. ; Kassis, S. ; Kumar, S. ; Badger, A. ; Adams, J. L. p38 mitogen-activated protein kinase inhibitors – mechanisms and therapeutic potentials. Pharmacol. Ther. 1999, 82, 389–397.
Lee, J. C. ; Laydon, J. T. ; McDonnell, P. C. ; Gallagher, T. F. ; Kumar, S. ; Green, D. ; McNulty, D. ; Blumenthal, M. J. ; Heyes, J. R. ; Landvatter, S. W. ; Strickler, J. E. ; McLaughlin, M. M. ; Siemens, I. R. ; Fisher, S. M. ; Livi, G. P. ; White, J. R. ; Adams, J. L. ; Young, P. R. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 1994, 372, 739–746
Lee, M. R. .; Kollman, P. A. Free-energy calculations highlight differences in accuracy between X-ray and NMR structures and add value to protein structure prediction. Structure 2001, 9(10), 905–916.
Lee, M. S. ; Olson, M. A. Calculation of absolute protein-ligand binding affinity using path and endpoint approaches. Biophys J. 2006, 90, 864–877.
Lee, M. S. ; Olson, M. A. Calculation of absolute protein-ligand binding affinity using path and endpoint approaches. Biophys. J. 2006, 90, 864–877.
Lee, P. H. ; Cucurull-Sanchez, L. ; Lu, J. ; Du, Y. J. Development of in silico models for human liver microsomal stability. J. Comput. Aided Mol. Des. 2007, 21, 665.
Leeson, P. D. ; Davis, A. M. Time-related differences in the physical property profiles of oral drugs. J. Med. Chem. 2004, 47, 6338.
Leeson, P. D. ; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat. Rev. Drug Discov. 2007, 6, 881–890.
Leftheris, K. ; Ahmed, G. ; Chan, R. ; Dyckman, A. J. ; Hussain, Z. ; Ho, K. ; Hynes, J., Jr. ; Letourneau, J. ; Li, W. ; Lin, S. ; Metzger, A. ; Moriarty, K. J. ; Riviello, C. ; Shimshock, Y. ; Wen, J. ; Wityak, J. ; Wrobleski, S. T. ; Wu, H. ; Wu, J. ; Desai, M. ; Gillooly, K. M. ; Lin, T. H. ; Loo, D. ; McIntyre, K. W. ; Pitt, S. ; Shen, D. R. ; Shuster, D. J. ; Zhang, R. ; Diller, D. ; Doweyko, A. ; Sack, J. ; Baldwin, J. ; Barrish, J. ; Dodd, J. ; Henderson, I. ; Kanner, S. ; Schieven, G. L. ; Webb, M. The discovery of orally active triaminotriazine aniline amides as inhibitors of p38 MAP kinase J. Med. Chem. 2004, 47, 6283–6291.
Lehikoinen, P. ; Sinnott, M. ; Krenitsky, T. Investigation of alpha-deuterium kinetic isotope effects on the purine nucleoside phosphorylase reaction by the equilibrium-perturbation technique. Biochem. J. 1989, 257, 355–359.
Leitgeb, M. ; Schröder, C. ; Boresch, S. Alchemical free energy calculations and multiple conformational substates. J. Chem. Phys. 2005, 122, 084109.
Leo, A. J. ; Hansch, C. Role of hydrophobic effects in mechanistic QSAR. Perspectives in Drug Discov. Des. 1999, 17, 1–25.
Lepre, C. A. ; et al. Applications of SHAPES screening in drug discovery. Comb. Chem. High Throughput Screen. 2002, 5, 583–590.
Lepre, C. A. ; Moore, J. M. ; Peng, J. W. Theory and applications of NMR-based screening in pharmaceutical research. Chem. Rev. 2004, 104(8), 3641–3676.
Lepre, C. A. ; Moore, J. M. ; Peng, J. W. Theory and applications of NMR-based screening in pharmaceutical research. Chem. Rev. 2004, 104, 3641–3676.
Lepre, C. A. Library design for NMR-based screening. Drug. Discov. Today 2001, 6, 133–140.
Lepre, C. A. Strategies for NMR screening and library design. In: BioNMR Techniques in Drug Research, Zerbe, O. ; Ed. Weinheim: Wiley-VCH; 2002, 1349–1364.
Lesuisse, D. ; et al. SAR and X-ray. A new approach combining fragment-based screening and rational drug design: application to the discovery of nanomolar inhibitors of Src SH2. J. Med. Chem. 2002, 45, 2379–2387.
Lesuisse, D. ; Lange, G. ; Deprez, P. ; Benard, D. ; Schoot, B. ; Delettre, G. ; Marquette, J.-P. ; Broto, P .; et al. SAR and X-ray: a new approach combining fragment-based screening and rational drug design: application to the discovery of nanomolar inhibitors of Src SH2. J. Med. Chem. 2002, 45, 2379–2387.
Levy, R. M. ; Zhang, L. Y. ; Gallicchio, E. ; Felts, T. On the nonpolar hydration free energy of proteins: surface area and continuum solvent models for the solute-solvent interaction energy. J. Am. Chem. Soc. 2003, 125, 9523–9530.
Lewandowicz, A. ; Ringia, E. ; Ting, L. ; Kim, K. ; Tyler, P. ; Evans, G. ; Zubkova, O. ; Mee, S. ; Painter, G. ; Lenz, D. ; Furneaux, R. ; Schramm, V. Energetic mapping of transition state analogue interactions with human and Plasmodium falciparum purine nucleoside phosphorylases. J. Biol. Chem. 2005, 280, 30320–30328.
Lewandowicz, A. ; Schramm, V. Transition state analysis for human and Plasmodium falciparum purine nucleoside phosphorylases. Biochemistry 2004, 43, 1458–1468.
Lewandowicz, A. ; Shi, W. X. ; Evans, G. B. ; Tyler, P. C. ; Furneaux, R. H. ; Basso, L. A. ; Santos, D. S. ; Almo, S. C. ; Schramm, V. L. Over-the-barrier transition state analogues and crystal structure with mycobacterium tuberculosis purine nucleoside phosphorylase. Biochemistry 2003, 42, 6057–6066.
Lewandowicz, A. ; Tyler, P. C. ; Evans, G. B. ; Furneaux, R. H. ; Schramm, V. L . Achieving the ultimate physiological goal in transition state analogue inhibitors for purine nucleoside phosphorylase. J. Biol. Chem. 2003, 278, 31465–31468.
Lewell, X. Q. ; Judd, D. B. ; Watson, S. P. ; Hann, M. M. RECAP – retrosynthetic combinatorial analysis procedure: a powerful new technique for identifying privileged molecular fragments with useful applications in combinatorial chemistry. J. Chem. Inf. Comput. Sci. 1998, 38, 511–522.
Lewin, J. L. ; Cramer, C. J. Rapid quantum mechanical models for the computational estimation of C-H bond dissociation energies as a measure of metabolic stability. Mol. Pharm. 2004, 1, 128.
Lewis, A. ; Glantz, M. Bovine brain purine-nucleoside phosphorylase purification, characterization, and catalytic mechanism. Biochemistry 1976, 15, 4451–4457.
Lewis, A. ; Lowy, B . Human erythrocyte purine nucleoside phosphorylase: molecular weight and physical properties: a Theorell-Chance catalytic mechanism. J. Biol. Chem. 1979, 254, 9927–9932.
Lewis, D. F. V. ; Ito, Y. ; Goldfarb, P. S. Structural modeling of the human drug-metabolizing cytochromes P 450. Curr. Med. Chem. 2006, 13, 2645.
Lewis, D. F. V. ; Lake, B. G. ; Dickins, M. ; Goldfarb, P. S. Homology modelling of CYP3A4 from the CYP2C5 crystallographic template: analysis of typical CYP3A4 substrate interactions. Xenobiotica 2004, 34, 549.
Li, C. ; Xu, L. ; Wolan, D. W. ; Wilson, I. A. ; Olson, A. J. Virtual screening of human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase against the NCI diversity set by use of Autodock to identify novel nonfolate inhibitors. J. Med. Chem. 2004, 47, 6681–6690.
Li, D. ; DeRose, E. F. ; London, R. E. The inter-ligand Overhauser effect: a powerful new NMR approach for mapping structural relationships of macromolecular ligands. J. Biomol. NMR 1999, 15, 71–76.
Li, H. ; Fajer, M. ; Yang, W. Simulated scaling method for localized enhanced sampling and simultaneous “alchemical” free energy simulations: a general method for molecular mechanical, quantum mechanical, and quantum mechanical/molecular mechanical simulations. J. Chem. Phys. 2007, 126, 024106.
Li, H. ; Sutter, J. ; Hoffmann, R. HypoGen: an automated system for generating 3d predictive pharmacophore models. In: Pharmacophore Perception, Development and Use in Drug Design, Güner, O. F. ; Ed. La Jolla, CA: International University Line; 2000, 173–189.
Li, H. ; Yang, W. Forging the missing link in free energy estimations: lambda-WHAM in thermodynamic integration, overlap histogramming, and free energy perturbation. Chem. Phys. Lett. 2007, 440(1–3), 155–159.
Li, J. ; Ehlers, T. ; Sutter, J. ; Varma-O' Brien, S. ; Kirchmair, J. CAESAR: a new conformer generation algorithm based on recursive buildup and local rotational consideration. J. Chem. Inf. Model. 2007, 47, 1923–1932.
Li, L. ; Dantzer, J. J. ; Nowacki, J. ; O'Callaghan, B. J. ; Meroueh, S. O. PDBCAL: a comprehensive dataset for receptor-ligand interactions with three-dimensional structures and binding thermodynamics from isothermal titration calorimetry. Chem. Bio. Drug Des. 2008, 71(6), 529–532.
Li, Y. ; Goddard, W. A. Prediction of the Structure of G-Protein Coupled Receptor with Application for Drug Design. Pac. Symp. Biocomput. 2008, 13, 344.
Liang, T. J. ; Heller, T. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells. Gastroenterology 2004, 127, S62–S71.
Liao, C. ; Karki, R. G. ; Marchand, C. ; Pommier, Y. ; Nicklaus, M. C. Virtual screening application of a model of full-length HIV-1 integrase complexed with viral DNA. Bioorg. Med. Chem. Lett. 2007, 17, 5361–5365.
Lieberman, R. L. ; Wustman, B. A. ; Huertas, P. ; Powe, A. C., Jr. ; Pine, W. P. ; Khanna, R. ; Schlossmacher, G. ; Ringe, D. ; Petsko, G. A. Structure of acid beta-glucosidase with pharmacological chaperone provides insight into Gaucher disease. Nat. Chem. Biol. 2007, 3, 101–107.
Lienhard, G. Enzymatic catalysis and transition-state theory. Science 1973, 180, 149–154.
Liepinsh, E. ; Otting, G. Organic solvents identify specific ligand binding sites on protein surfaces. Nat. Biotechnol. 1997, 15, 264–268.
Lightstone, F. C. ; Bruice, T. C. Ground state conformations and entropic and enthalpic factors in the efficiency of intramolecular and enzymatic reactions. 1. Cyclic anhydride formation by substituted glutarates, succinate, and 3,6-endoxo-Δ4-tetrahydrophthalate monophenyl esters. J. Am. Chem. Soc. 1996, 118, 2595–2605.
Lin, J. H. ; Yamazaki, M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin. Pharmacokinet. 2003, 42, 59.
Lin, M. L. ; Shapiro, M. J. ; Wareing, J. R. Diffusion-edited NMR: affinity NMR for direct observation of molecular interactions. J. Am. Chem. Soc. 1997, 119, 5349–5250.
Lin, T. H. ; Metzger, A. ; Diller, D. J. ; Desai, M. ; Henderson, I. ; Ahmed, G. ; Kimble, E. F. ; Quadros, E. ; Webb, M. L. Discovery and characterization of triaminotriazine aniline amides as highly selective p38 kinase inhibitors. J. Pharmacol. Exp. Ther. 2006, 318, 495–502.
Lipinski, C. A. ; Lombardo, F. ; Dominy, B. W. ; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 1997, 23, 3.
Lipinski, C. A. ; Lombardo, F. ; Dominy, B. W. ; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 2001, 46, 3–26.
Lipinski, C. A. ; Lombardo, F. ; Dominy, B. W. ; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Drug Deliv. Res. 1997, 23, 3–25.
Lipinski, C. A. ; Lombardo, F. ; Dominy, B. W. ; Feeny, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 1997, 23, 3–25.
Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Meth. 2000, 44, 235.
Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 2000, 44, 235–249.
Liu, C. ; Lin, J. ; Pitt, S. ; Zhang, R. F. ; Sack, J. S. ; Kiefer, S. E. ; Kish, K. ; Doweyko, A. M. ; Zhang, H. ; Marathe, P. H. ; Trzaskos, J. ; McKinnon, M. ; Dodd, J. H. ; Barrish, J. C. ; Schieven, G. L. ; Leftheris, K. Benzothiazole based inhibitors of p38α MAP kinase. Bioorg. Med. Chem. Lett. 2008, 18, 1874–1879.
Liu, C. ; Wrobleski, S. T. ; Lin, J. ; Ahmed, G. ; Metzger, A. ; Wityak, J. ; Gillooly, K. M. ; Shuster, D. J. ; McIntyre, K. W. ; Pitt, S. ; Shen, D. R. ; Zhang, R. F. ; Zhang, H. ; Doweyko, A. M. ; Diller, D. ; Henderson, I. ; Barrish, J. C. ; Dodd, J. H. ; Schieven, G. L. ; Leftheris, K. 5-Cyanopyrimidine derivatives as a novel class of potent, selective, and orally active inhibitors of p38α MAP kinase. J. Med. Chem. 2005, 48, 6261–6270.
Liu, F. L. ; et al. Mechanism of drug resistance revealed by the crystal structure of the unliganded HIV-1 protease with F53L mutation. J. Mol. Biol. 2006, 358(5), 1191–1199.
Liu, H. ; Li, Y. ; Song, M. ; Tan, X. ; Cheng, F. ; Zheng, S. ; Shen, J. ; Luo, X. ; Ji, R. ; Yue, J. ; Hu, G. ; Jiang, H. ; Chen, K. Structure-based discovery of potassium channel blockers from natural products: virtual screening and electrophysiological assay testing. Chemistry 2003, 10, 1103–1113.
Liu, J. ; Yang, L. ; Li, Y. ; Pan, D. ; Hopfinger, A. J. Constructing plasma protein binding model based on a combination of cluster analysis and 4D-fingerprint molecular similarity analyses. Bioorg. Med. Chem. 2006, 14, 611.
Liu, J.-S. ; Cheng, W.-C. ; Wang, H.-J. ; Chen, Y.-C. ; Wang, W.-C. Structure-based inhibitor discovery of Helicobacter pylori dehydroquinate synthase. Biochem. Biophys. Res. Commun. 2008, 373, 1–7.
Liu, X. ; Tu, M. ; Kelly, R. S. ; Chen, C. ; Smith, B. J. Development of a computational approach to predict blood-brain barrier permeability. Drug Metab. Dispos. 2004, 32, 132.
Liu, Z. ; Huang, C. ; Fan, K. ; Wei, P. ; Chen, H. ; Liu, S. ; Pei, J. ; Shi, L. ; Li, B. ; Yang, K. ; Liu, Y. ; Lai, L. Virtual screening of novel noncovalent inhibitors for SARS-CoV 3C-like proteinase. J. Chem. Inf. Model. 2005, 45, 10–17.
Liverton, N. J. ; Holloway, M. K. ; McCauley, J. A. ; Rudd, M. T. ; Butcher, J. W. ; Carroll, S. S. ; DiMuzio, J. ; Fandozzi, C. ; Gilbert, K. F. ; Mao, S. S. ; McIntyre, C. J. ; Nguyen, K. T. ; Romano, J. J. ; Stahlhut, M. ; Wan, B. L. ; Olsen, D. B. ; Vacca, J. P. Molecular modeling based approach to potent P2-P4 macrocyclic inhibitors of hepatitis C NS3/4A protease. J. Am. Chem. Soc. 2008, 130, 4607–4609.
Llinas-Brunet, M. ; Bailey, M. D. ; Bolger, G. ; Brochu, C. ; Faucher, A. M. ; Ferland, J. M. ; Garneau, M. ; Ghiro, E. ; Gorys, V. ; Grand-Maitre, C. ; Halmos, T. ; Lapeyre-Paquette, N. ; Liard, F. ; Poirier, M. ; Rheaume, M. ; Tsantrizos, Y. S. ; Lamarre, D. Structure-activity study on a novel series of macrocyclic inhibitors of the hepatitis C virus NS3 protease leading to the discovery of BILN 2061. J. Med. Chem. 2004, 47, 1605–1608.
Lobell, M. ; Hendrix, M. ; Hinzen, B. ; Keldenich, J. ; Meier, H. ; Schmeck, C. ; Schohe-Loop, R. ; Wunberg, T. ; Hillisch, A. In silico ADMET traffic lights as a tool for the prioritization of HTS hits. ChemMedChem 2006, 1, 1229.
Lobell, M. ; Molnar, L. ; Keseru, G. M. Recent advances in the prediction of blood-brain partitioning from molecular structure. J. Pharm. Sci. 2003, 92, 360.
Lobley, C. M. ; et al. The crystal structure of Escherichia coli ketopantoate reductase with NADP+ bound. Biochemistry 2005, 44, 8930–8939.
Logsdon, B. C. ; et al. Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity. J. Virol. 2004, 78(6), 3123–3132.
Lombardo, F. ; Obach, R. S. ; DiCapua, F. ; Bakken, G. A. ; Lu, J. ; Potter, D. M. ; Gao, F. ; Miller, M. D. ; Zhang, Y. A hybrid mixture discriminant analysis-random forest computational model for the prediction of volume of distribution of drugs in human. J. Med. Chem. 2006, 49, 2262.
Lu, J. ; Bakken, G. A. Building classification models for DMSO solubility: comparison of five methods. 228th ACS National Meeting, Philadelphia, PA, United States, August 22–26, 2004, CINF-045.
Lu, N. D. ; Singh, J. K. ; Kofke, D. A. Appropriate methods to combine forward and reverse free-energy perturbation averages. J. Chem. Phys. 2003, 118(7), 2977–2984.
Lu, Y. ; Wang, C.-Y. ; Wang, S. Binding free energy contributions of interfacial waters in HIV-1 protease/inhibitor complexes. J. Am. Chem. Soc. 2006, 128, 11830–11839.
Lu, Z. ; Bohn, J. ; Bergeron, R. ; Deng, Q. ; Ellsworth, K. P. ; Geissler, W. M. ; Harris G. ; McCann, P. E. ; McKeever, B. ; Myers, R. W. ; Saperstein, R. ; Willoughby, C. A. ; Yao, J. ; Chapman, K. A. A New class of glycogen phosphorylase inhibitors. Bioorg. Med. Chem. Lett. 2003, 13, 4125–4128.
Luecke, H. ; Richter, H. T. ; Lanyi, J. K. Proton transfer pathways in bacteriorhodopsin at 2.3 angstrom resolution. Science, 1998, 280, 1934.
Luecke, H. ; Schobert, B. ; Richter, H. T. ; Cartailler, J. P. ; Lanyi, J. K. Structure of Bacteriorhodopsin at 1.55 Å Resolution. J. Mol. Biol., 1999, 291, 899.
Lugovskoy, A. A. ; et al. A novel approach for characterizing protein ligand complexes: molecular basis for specificity of small-molecule Bcl-2 inhibitors. J. Am. Chem. Soc. 2002, 124, 1234–1240.
Luo, H. ; Sharp, K. On the calculation of absolute macromolecular binding free energies. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 10399–10404.
Luque, I. ; et al. Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis. Biochemistry 1998, 37(17), 5791–5797.
Luzhkov, V. B. ; Selisko, B. ; Nordqvist, A. ; Peyrane, F. ; Decroly, E. ; Alvarez, K. ; Karlen, A. ; Canard, B. ; Aaqvist, J. Virtual screening and bioassay study of novel inhibitors for dengue virus mRNA cap (nucleoside-2′O)-methyltransferase. Bioorg. Med. Chem. 2007, 15, 7795–7802.
Lyne, P. D. ; Kenny, P. W. ; Cosgrove, D. A. ; Deng, C. ; Zabludoff, S. ; Wendoloski, J. J. ; Ashwell, S. Identification of compounds with nanomolar binding affinity for checkpoint kinase-1 using knowledge-based virtual screening. J. Med. Chem. 2004, 47, 1962–1968.
Lyne, P. D. Structure-based virtual screening: an overview. Drug Disc. Today 2002, 7, 1047–1055.
Méndez, R. ; Leplae, R. ; Lesink, M. F. ; Wodak, S. J. Assessment of CAPRI predictions in rounds 3-5 shows progress in docking procedures. Proteins 2005, 60(2), 150–169.
Möhle, K. ; Hofmann, H. J. ; Thiel, W. Description of peptide and protein secondary structures employing semiempirical methods. J. Comput. Chem. 2001, 22, 509–520.
Müller, G . Towards 3D Structures of G Protein-Coupled Receptors: A Multidisciplinary Approach. Curr. Med. Chem. 2000, 7, 861.
MacKerell, A. D., Jr. ; Bashford, D. ; Bellott, M. ; Dunbrack, R. L. ; Evanseck, J. D. ; Field, M. J. ; Fischer, S. ; Gao, J. ; Guo, H. ; Ha, S. ; Joseph-McCarthy, D. ; Kuchnir, L. ; Kuczera, K. ; Lau, F. T. K. ; Mattos, C. ; Michnick, S. ; Ngo, T. ; Nguyen, D. T. ; Prodhom, B. ; Reiher, W. E., III ; Roux, B. ; Schlenkrich, M. ; Smith, J. C. ; Stote, R. ; Straub, J. ; Watanabe, M. ; Wiorkiewicz-Kuczera, J. ; Yin, D. ; Karplus, M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 1998, 102(18), 3586–3616.
Maggiora, G. M. On outliers and activity cliffs: why QSAR often disappoints. J. Chem. Inf. Model. 2006, 46, 1535.
MaloneyHuss, K. ; Lybrand, T. P. Three-dimensional structure for the β2 adrenergic receptor protein based on computer modeling studies. J. Mol. Biol. 1992, 225, 859.
Malvezzi, A. ; de Rezende, L. ; Izidoro, M. A. ; Cezari, M. H. S. ; Juliano, L. ; Amaral, A. T. Uncovering false positives on a virtual screening search for cruzain inhibitors. Bioorg. Med. Chem. Lett. 2008, 18, 350–354.
Mandel, J. Use of the singular value decomposition in regression-analysis. Am. Stat. 1982, 36, 15–24.
Manetti, F. ; Falchi, F. ; Crespan, E. ; Schenone, S. ; Maga, G. ; Botta, M. N-(thiazol-2-yl)-2-thiophene carboxamide derivatives as Abl inhibitors identified by a pharmacophore-based database screening of commercially available compounds. Bioorg. Med. Chem. Lett. 2008, 18, 4328–4331.
Mann, G. ; Hermans, J. Modeling protein-small molecule interactions: structure and thermodynamics of noble gases binding in a cavity in mutant phage T4 lysozyme L99A. J. Mol. Biol. 2000, 302, 979–989.
Mao, C. ; Cook, W. J. ; Zhou, M. ; Federov, A. A. ; Almo, S. C. ; Ealick, S. E. Calf spleen purine nucleoside phosphorylase complexed with substrates and substrate analogues. Biochemistry 1998, 37, 7135–7146.
Mao, H. Z. ; Weber, J. Identification of the betatp site in the x-ray structure of f1-atpase as the high-affinity catalytic site. Proc. Natl. Acad. Sci. U.S.A. 2007, 104(47), 18478–18483.
Mao, S. S. ; DiMuzio, J. ; McHale, C. ; Burlein, C. ; Olsen, D. ; Carroll, S. S. A time-resolved, internally quenched fluorescence assay to characterize inhibition of hepatitis C virus nonstructural protein 3-4A protease at low enzyme concentrations. Anal. Biochem. 2008, 373, 1–8.
Marchetti, A. ; Ontoria, J. M. ; Matassa, V. G. Synthesis of Two Novel Cyclic Biphenyl Ether Analogs of an Inhibitor of HCV NS3 Protease. Synlett 1999, S1, 1000–1002.
Mardis, K. L. ; Luo, R. ; Gilson, M. K. Interpreting trends in the binding of cyclic ureas to HIV-1 protease. J. Mol. Biol. 2001, 309, 507–517.
Markert, M. ; Finkel, B. ; McLaughlin, T. ; Watson, T. ; Collard, H. ; McMahon, C. ; Andrews, L. ; Barrett, M. ; Ward, F. Mutations in purine nucleoside phosphorylase deficiency. Hum. Mutat. 1997, 9, 118–121.
Markert, M. Purine nucleoside phosphorylase deficiency. Immunodef. Rev. 1991, 3, 45–81.
Markt, P. ; Schuster, D. ; Kirchmair, J. ; Laggner, C. ; Langer, T. Pharmacophore modeling and parallel screening for PPAR ligands. J. Comput. Aided Mol. Des. 2007, 21, 575–590.
Marqusee, S. ; Robbins, V. H. ; Baldwin, R. L. Unusually stable helix formation in short alanine-based peptides. Proc. Natl. Acad. Sci. U.S.A. 1989, 86(14), 5286–5290.
Marshall, G. R. ; Barry, C. D. ; Bosshard, H. E. ; Dammkoehler, R. A. ; Dunn, D. A. The conformational parameter in drug design: the active analog approach. In: Computer-Assisted Drug Design, Olson, E. C. ; Christoffersen, R. E. ; Eds. Washington, D.C.: American Chemical Society; 1979, 205–226.
Marti-Renom, M. A. ; Madhusudhan, M. S. ; Fiser, A. ; Rost, B. ; Sali, A. Reliability of assessment of protein structure prediction methods. Structure 2002, 10(3), 435–440.
Martin, P. ; et al. “Wide-open” 1.3 A structure of a multidrug-resistant HIV-1 protease as a drug target. Structure 2005, 13(12), 1887–1895.
Martin, P. ; et al. “Wide-open” 1.3 angstrom structure of a multidrug-resistant HIV-1 protease as a drug target. Structure 2005, 13(12), 1887–1895.
Martin, W. H. ; Hoover, D. J. ; Armento, S. J. ; Stock, I. A. ; McPherson, R. K. ; Danley, D. E. ; Stevenson, R. W. ; Barrett, E. J. ; Treadway, J. L. Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 1776–1781.
Martin, Y. ; Bures, M. ; Danaher, E. ; DeLazzer, J. New strategies that improve the efficiency of the 3D design of bioactive molecules. In: Trends in QSAR and Molecular Modelling 92, Wermuth, C. ; Ed. Leiden: ESCOM; 1993, 20–26.
Martin, Y. C. Distance comparisons (DISCO): a new strategy for examining 3d structure-activity relationships. In: Classical and 3D QSAR in Agrochemistry, Hansch, C. , Fujita, T. ; Ed. Washington, D.C.: American Chemical Society; 1995, 318–329.
Mason, J. S. ; Good, A. C. ; Martin, E. J. 3D pharmacophores in drug discovery. Curr. Pharm. Des. 2001, 7, 567–597.
Massova, I. ; Kollman, P. A. Computational alanine scanning to probe protein-protein interactions: a novel approach to evaluate binding free energies. J. Am. Chem. Soc. 1999, 121, 8133–8143.
Matter, H. Selecting optimally diverse compounds from structure databases: a validation study of two-dimensional and three-dimensional molecular descriptors. J. Med. Chem. 1997, 40, 1219–1229.
Matthews, B. W. J. Mol. Biol. 1968, 33, 491–497.
Mattos, C. ; Bellamacina, C. R. ; Peisach, E. ; Vitkup, D. ; Petsko, G. A. ; Ringe, D. Multiple solvent crystal structures: probing binding sites, plasticity and hydration. J. Mol. Biol. 2006, 357, 1471–1482.
Mattos, C. ; Ringe, D. Locating and characterizing binding sites on proteins. Nat. Biotechnol. 1996, 14, 595–599.
Mavunkel, B. J. ; Chakravarty, S. ; Perumattam, J. J. ; Luedtke, G. R. ; Liang, X. ; Lim, D. ; Xu, Y.-J. ; Laney, M. ; Liu, D. Y. ; Schreiner, G. F. ; Lewicki, J. A. ; Dugar, S. Indole-based heterocyclic inhibitors of p38α MAP kinase: designing a conformationally restricted analogue. Bioorg. Med. Chem. Lett. 2003, 13, 3087–3090.
Maybridge . http://www.daylight.com/products/databases/Maybridge.html 2005.
Mayer, D. ; Naylor, C. B. ; Motoc, I. ; Marshall, G. R. A unique geometry of the active site of angiotensin-converting enzyme consistent with structure-activity studies. J. Comput. Aided Mol. Des. 1987, 1, 3–16.
Mayer, M. ; Meyer, B. Characterization of ligand binding by saturation transfer difference NMR spectroscopy. Angew. Chem. Int. Ed. 1999, 38, 1784–1788.
McCammon, J. A. Computer-aided molecular design. Science 1987, 238, 486–491.
McCammon, J. A. Target flexibility in molecular recognition. Biochim. Biophys. Acta 2005, 1754(1–2), 221–224.
McCann, J. ; Berti, P. Transition state analysis of acid-catalyzed dAMP hydrolysis. J. Am. Chem. Soc. 2007, 129, 7055–7064.
McClure, K. F. ; Letavic, M. A. ; Kalgutkar, A. S. ; Gabel, C. A. ; Audoly, L. ; Barberia, J. T. ; Braganza, J. F. ; Carter, D. ; Carty, T. J. ; Cortina, S. R. ; Dombroski, M. A. ; Donahue, K. M. ; Elliott, N. C. ; Gibbons, C. P. ; Jordan, C. K. ; Kuperman, A. V. ; Labasi, J. M. ; LaLiberte, R. E. ; McCoy, J. M. ; Naiman, B. M. ; Nelson, K. L. ; Nguyen, H. T. ; Peese, K. M. ; Sweeney, F. J. ; Taylor, T. J. ; Trebino, C. E. ; Abramov, Y. A. ; Laird, E. R. ; Volberg, W. A. ; Zhou, J. ; Bach, J. ; Lombardo, F. Structure-activity relationships of triazolopyridine oxazole p38 inhibitors: identification of candidates for clinical development. Bioorg. Med. Chem. Lett. 2006, 16, 4339–4344.
McCoy, M. A. ; Wyss, D. F. , Spatial localization of ligand binding sites from electron current density surfaces calculated from NMR chemical shift perturbations. J. Am. Chem. Soc. 2002, 124(39), 11758–11763.
McCoy, M. A. ; Wyss, D. F. Alignment of weakly interacting molecules to protein surfaces using simulations of chemical shift perturbations. J. Biomol. NMR 2000, 18, 189–198.
McCoy, M. A. ; Wyss, D. F. Spatial localization of ligand binding sites from electron current density surfaces calculated from NMR chemical shift perturbations. J. Am. Chem. Soc. 2002, 124, 11758–11763.
McGaughey, G. B. ; Sheridan, R. P. ; Bayly, C. I. ; Culberson, J. C. ; Kreatsoulas, C. ; Lindsley, S. ; Maiorov, V. ; Truchon, J. F. ; Cornell, W. D. Comparison of topological, shape, and docking methods in virtual screening. J. Chem. Inf. Model. 2007, 47, 1504–1519.
McGaughey, G. B. ; Sheridan, R. P. ; Bayly, C. I. ; Culberson, J. C. ; Kreatsoulas, C. ; Lindsley, S. ; Maiorov, V. ; Truchon, J.-F. ; Cornell, W. D. Comparison of topological, shape, and docking methods in virtual screening. J. Chem. Inf. Model. 2007, 47(4), 1504–1519.
McGregor, M. J. ; Muskal, S. M. Pharmacophore fingerprinting. 1. Application to QSAR and focused library design. J. Chem. Inf. Comput. Sci. 1999, 39, 569–574.
McNally, V. A. ; Gbaj, A. ; Douglas, K. T. ; Stratford, I. J. ; Jaffar, M. ; Freemanan, S. ; Bryce, R. A. Identification of a novel class of inhibitor of human and Escherichia coli thymidine phosphorylase by in silico screening. Bioorg. Med. Chem. Lett. 2003, 13, 3705–3709.
Meagher, K. L. ; Carlson, H. A. Solvation influences flap collapse in HIV-1 protease. Proteins 2005, 58(1), 119–125.
Medek, A. ; Hajduk, P. J. ; Mack, J. ; Fesik, S. W. The use of differential chemical shifts for determining the binding site location and orientation of protein-bound ligands. J. Am. Chem. Soc. 2000, 122, 1241–124.
Medina-Franco, J. L. ; Golbraikh, A. ; Oloff, S. ; Castillo, R. ; Tropsha, A. Quantitative structure-activity relationship analysis of pyridinone HIV-1 reverse transcriptase inhibitors using the k nearest neighbor method and QSAR-based database mining. J. Comput. Aided Mol. Des. 2005, 19, 229–242.
Meinecke, R. ; Meyer, B. Determination of the binding specificity of an integral membrane protein by saturation transfer difference NMR: RGD peptide ligands binding to integrin αIIbβ. J. Am. Chem. Soc. 2001, 44, 3059–3065.
Meirovitch, H. Recent developments in methodologies for calculating the entropy and free energy of biological systems by computer simulation. Curr. Opin. Struc. Biol. 2007, 17, 181–186.
Melander, L. ; Saunders, W. H., Jr. Reaction Rates of Isotopic Molecules. New York, NY: Wiley & Sons; 1980.
Mente, S. R. ; Lombardo, F. A recursive-partitioning model for blood-brain barrier permeation. J. Comput. Aided Mol. Design 2005, 19, 465.
Mervis, J. Productivity counts – but the definition is key. Science 2005, 309, 726.
Merz, K. M. ; Kollman, P. A. Free energy perturbation simulations of the inhibition of thermolysin: prediction of the free energy of binding of a new inhibitor. J. Am. Chem. Soc. 1989, 111, 5649–5658.
Meyer, B. , Peters, T. NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors. Angew. Chem. Int. Ed. Engl. 2003, 42(8), 864–890.
Michel, J. ; Verdonk, M. L. ; Essex, J. W. Protein-ligand binding free energy predictions by implicit solvent simulation: a tool for lead optimization? J. Med. Chem. 2006, 49, 7427–7439.
Migliaccio, G. ; Tomassini, J. E. ; Carroll, S. S. ; Tomei, L. ; Altamura, S. ; Bhat, B. ; Bartholomew, L. ; Bosserman, M. R. ; Ceccacci, A. ; Colwell, L. F. ; Cortese, R. ; De Francesco, R. ; Eldrup, A. B. ; Getty, K. L. ; Hou, X. S. ; LaFemina, R. L. ; Ludmerer, S. W. ; MacCoss, M. ; McMasters, D. R. ; Stahlhut, M. W. ; Olsen, D. B. ; Hazuda, D. J. ; Flores, O. A. Characterization of resistance to non-obligate chain-terminating ribonucleoside analogs that inhibit hepatitis C virus replication in vitro. J. Biol. Chem. 2003, 278, 49164–49170.
Miles, R. W. ; Tyler, P. C. ; Furneaux, R. H. ; Bagdassarian, C. K. ; Schramm, V. L. One-third-the-sites transition-state inhibitors for purine nucleoside phosphorylase. Biochemistry 1998, 37, 8615–8621.
Miller, M. ; et al. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3-a resolution. Science 1989, 246(4934), 1149–1152.
Miller, M. D. ; Kearley, S. K. ; Underwood, D. J. ; Sheridan, R. P. J. FLOG: a system to select ‘quasi-flexible' ligands complementary to a receptor of known three-dimensional structure. Comput. Aided Mol. Des. 1994, 8, 153–174.
Miller, M. D. ; Sheridan, R. P. ; Kearsley, S. K. SQ: a program for rapidly producing pharmacophorically relevent molecular superpositions. J. Med. Chem. 1999, 42, 1505–1514.
Min, D. ; Li, H. ; Li, G. ; Bitetti-Putzer, R. ; Yang, W. Synergistic approach to improve “alchemical” free energy calculation in rugged energy surface. J. Chem. Phys. 2007, 126(14), 144109.
Min, D. ; Yang, W. Energy difference space random walk to achieve fast free energy calculations. J. Chem. Phys. 2008, 128(19).
Mizutani, M. Y. ; Itai, A. Efficient method for high-throughput virtual screening based on flexible docking: discovery of novel acetylcholinesterase inhibitors. J. Med. Chem. 2004, 47, 4818–4828.
Mlinsek, G. ; Novic, M. ; Hodoscek, M. ; Solmajer, T. Prediction of enzyme binding: human thrombin inhibition study by quantum chemical and artificial intelligence methods based on X-ray structures. J. Chem. Inf. Comput. Sci. 2001, 41(5), 1286–1294.
Mobley, D. L. ; Chodera, J. D. ; Dill, K. A. Confine-and-release method: obtaining correct binding free energies in the presence of protein conformational change. J. Chem. Theory Comput. 2007, 3(4), 1231–1235.
Mobley, D. L. ; Chodera, J. D. ; Dill, K. A. On the use of orientational restraints and symmetry corrections in alchemical free energy calculations. J. Chem. Phys. 2006, 125, 084902.
Mobley, D. L. ; Dill, K. A. ; Chodera, J. D. Treating entropy and conformational changes in implicit solvent simulations of small molecules. J. Phys. Chem. B 2008, 112, 938–946.
Mobley, D. L. ; Dill, K. A. Binding of small-molcule ligand to proteins. “What you see” is not always “what you get.” Structure 2009, 17, 489–498.
Mobley, D. L. ; Dumont, È. ; Chodera, J. D. ; Dill, K. A. Comparison of charge models for fixed-charge force fields: small-molecule hydration free energies in explicit solvent. J. Phys. Chem. B 2007, 111(9), 2242–2254.
Mobley, D. L. ; Graves, A. P. ; Chodera, J. D. ; McReynolds, A. C. ; Shoichet, B. K. ; Dill, K. A. Predicting absolute ligand binding free energies to a simple model site. J. Mol. Biol. 2007, 371(4), 1118–1134.
Mobley, D. L. Unpublished data.
MOE . http://www.chemcomp.com/fdept/prodinfo.htm#Cheminformatics. 2005.
Mohan, V. ; Gibbs, A. C. ; Cummings, M. D. ; Jaeger, E. P. ; DesJarlais, R. L. Docking: successes and challenges. Curr. Pharm. Des. 2005, 11, 323–333.
Mojumdar, S. C. ; Martiska, L. ; Valigura, D. ; Melnik, M. Thermal and spectral properties of halogenosalicylato-Cu(II) complexes. J. Therm. Analysis and Calor. 2003, 74, 905–914.
Montes, M. ; Braud, E. ; Miteva, M. A. ; Goddard, M.-L. ; Mondesert, O. ; Kolb, S. ; Brun, M.-P. ; Ducommun, B. ; Garbay, C. ; Villoutreix, B. O. Receptor-based virtual ligand screening for the identification of novel CDC25 phosphatase inhibitors. J. Chem. Inf. Model. 2008, 48, 157–165.
Moock, T. E. ; Henry, D. R. ; Ozkabak, A. G. ; Alamgir, M. Conformational searching in ISIS/3D databases. J. Chem. Inf. Comput. Sci. 1994, 34, 184–189.
Moore, J. M. NMR screening in drug discovery. Curr. Opin. Biotechnol. 1999, 10, 54–58.
Moore, J. P. ; Stevenson, M. New targets for inhibitors of HIV-1 replication. Nat. Rev. Mol. Cell Biol. 2000, 1(1), 40–49.
Morand, E. F. ; Leech, M. ; Bernhagen, J. MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis. Nat. Rev. Drug Discov. 2006, 5, 399–411.
Moreira, I. S. ; Fernandes, P. A. ; Ramos, M. J. Hot spots–a review of the protein-protein interface determinant amino-acid residues. Proteins 2007, 68, 803–812.
Morozov, A. V. ; Tsemekhman, K. ; Baker, D. Electron density redistribution accounts for half the cooperativity of alpha helix formation. J. Phys. Chem. B 2006, 110(10), 4503–4505.
Morphy, R. The influence of target family and functional activity on the physicochemical properties of pre-clinical compounds. J. Med. Chem. 2006, 49, 2969.
Morton, A. ; Baase, W. A. ; Matthews, B. W. Energetic origins of specificity of ligand binding in an interior nonpolar cavity of T4 lysozyme. Biochemistry 1995, 34, 8564–8575.
Morton, A. ; Matthews, B. W. Specificity of ligand binding in a buried nonpolar cavity of T4 lysozyme: linkage of dynamics and structural plasticity. Biochemistry 1995, 34, 8576–8588.
Moss, G. P. ; Cronin, M. T. D. Quantitative structure-permeability relationships for percutaneous absorption: re-analysis of steroid data. Int. J. Pharm. 2002, 238, 105–109.
Mozziconacci, J.-C. ; Arnoult, E. ; Bernard, P. ; Do, Q. T. ; Marot, C. ; Morin-Allory, L. Optimization and validation of a docking-scoring protocol and application to virtual screening for COX-2 inhibitors. J. Med. Chem. 2005, 48, 1055–1068.
Muegge, I. ; Enyedy, I. J. Virtual screening for kinase targets. Curr. Med. Chem. 2004, 11, 693–707.
Mukherjee, P. ; Desai, P. ; Ross, L. ; White, E. L. ; Avery, M. A. Structure-based virtual screening against SARS-3CLpro to identify novel non-peptidic hits. Bioorg. Med. Chem. 2008, 16, 4138–4149.
Mulholland, A. J. Modelling enzyme reaction mechanisms, specifity and catalysis. Drug. Discov. Today 2005, 10, 1393–1402.
Munns, A. ; Tollin, P. The crystal and molecular structure of inosine. Acta Crystallogr. B 1970, 26, 1101–1113.
Murali, N. ; Jarori, G. K. ; Landy, S. B. ; Rao, B. D. Two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY) studies of nucleotide conformations in creatine kinase complexes: effects due to weak nonspecific binding. Biochemistry 1993, 32, 12941–12948.
Murkin, A. ; Tyler, P. ; Schramm, V. Transition-state interactions revealed in purine nucleoside phosphorylase by binding isotope effects. J. Am. Chem. Soc. 2008, 130, 2166–2167.
Murkin, A. S. ; Birck, M. R. ; Rinaldo-Matthis, A. ; Shi, W. X. ; Taylor, E. A. ; Almo, S. C. ; Schramm, V. L. Neighboring group participation in the transition state of human purine nucleoside phosphorylase. Biochemistry 2007, 46, 5038–5049.
Murrall, N. W. ; Davies, E. K. Conformational freedom in 3-D databases. 1. Techniques. J. Chem. Inf. Comput. Sci. 1990, 30, 312–316.
Murray, C. W. ; Baxter, C. A. ; Frenkel, A. D. The sensitivity of the results of molecular docking to induced fit effects: application to thrombin, thermolysin and neuraminidase. J. Comput. Aided Mol. Des. 1999, 13, 547–562.
Murray, C. W. ; et al. Application of fragment screening by x-ray crystallography to beta-secretase. J. Med. Chem. 2007, 50, 1116–1123.
Murray, C. W. ; Verdonk, M. L. The consequences of translational and rotational entropy lost by small molecules on binding to proteins. J. Comput. Aided Mol. Des. 2002, 16, 741–753.
Naim, M. ; Bhat, S. ; Rankin, K. N. ; Dennis, S. ; Chowdhury, S. F. ; Siddiqi, I. ; Drabik, P. ; Sulea, T. ; Bayly, C. I. ; Jakalian, A. ; Purisima, E. O. Solvated interaction energy (sie) for scoring protein-ligand binding affinities. 1. Exploring the parameter space. J. Chem. Info. Model. 2007, 47(1), 122–133.
Navia, M. A. ; et al. 3-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1. Nature 1989, 337(6208), 615–620.
NCI . http://dtp nci nih gov/docs/3d_database/structural_information/smiles_strings html 2007.
Negron-Encarnacion, I. ; Arce, R. ; Jimenez, M. Characterization of acridine species adsorbed on (NH4)2SO4, SiO2, Al2O3, and MgO by steady-state and time-resolved fluorescence and diffuse reflectance techniques. J. Phys. Chem. A 2005, 109, 787–797.
Netzeva, T. I. ; Gallegos, S. A. ; Worth, A. P. Comparison of the applicability domain of a quantitative structure-activity relationship for estrogenicity with a large chemical inventory. Environ. Toxicol. Chem. 2006, 25, 1223–1230.
Netzeva, T. I. ; Schultz, T. W. QSARs for the aquatic toxicity of aromatic aldehydes from Tetrahymena data. Chemosphere 2005, 61, 1632–1643.
Nicholls, A. ; Mobley, D. L. ; Guthrie, P. J. ; Chodera, J. D. ; Pande, V. S. Predicting small-molecule solvation free energies: an informal blind test for computational chemistry. J. Med. Chem. 2008, 51, 769–779.
Nicholson, L. K. ; et al. Flexibility and function in HIV-1 protease. Nat. Struct. Biol. 1995, 2(4), 274–280.
Nicola, T. ; Brenner, M. ; Donsbach, K. ; Kreye, P. First Scale-Up to Production Scale of a Ring Closing Metathesis Reaction Forming a 15-Membered Macrocycle as a Precursor of an Active Pharmaceutical Ingredient. Org. Process Res. Dev. 2005, 9, 513–515.
Nienaber, V. I. ; Richardson, P. I. ; Klighofer, V. ; Bouska, J. J. ; Giranda, V. I. ; Greer J. Discovering novel ligands for macromolecules using x-ray crystallographic screening. Nat. Biotechnol. 2000, 18, 1105–1108.
Nienaber, V. L. ; et al. Discovering novel ligands for macromolecules using x-ray crystallographic screening. Nat. Biotechnol. 2000, 18, 1105–1108.
Nienaber, V. L. ; Richardson, P. L. ; Klighofer, V. ; Bouska, J. J. ; Giranda, V. L. ; Greer, J. Discovering novel ligands for macromolecules using X-ray crystallographic screening. Nat. Biotechnol. 2000, 18(10), 1105–1108.
Nikitina, E. ; Sulimov, D. ; Zayets, V. ; Zaitseva, N. Semiempirical calculations of binding enthalpy for protein-ligand complexes. Int. J. Quantum Chem. 2004, 97(2), 747–763.
Nilsson, K. ; Hersleth, H. P. ; Rod, T. H. ; Andersson, K. K. ; Ryde, U. The protonation status of compound II in myoglobin, studied by a combination of experimental data and quantum chemical calculations: quantum refinement. Biophys. J. 2004, 87(5), 3437–3447.
Nilsson, K. ; Ryde, U. Protonation status of metal-bound ligands can be determined by quantum refinement. J. Inorg. Biochem. 2004, 98(9), 1539–1546.
Niv, M. Y. ; Skrabanek, L. ; Filizola, M. ; Weinstein, H. Modeling activated states of GPCRs: the rhodopsin template. J. Comput. Aided Mol. Des. 2006, 20, 437.
Nolan, K. A. ; Timson, D. J. ; Stratford, I. J. ; Bryce, R. A. In silico identification and biochemical characterization of novel inhibitors of NQO1. Bioorg. Med. Chem. Lett. 2006, 16, 6246–6254.
Nordqvist, A. ; Nilsson, M. T. ; Roettger, S. ; Odell, L. R. ; Krajewski, W. W. ; Andersson, C. E. ; Larhed, M. ; Mowbray, S. L. ; Karlen, A. Evaluation of the amino acid binding site of Mycobacterium tuberculosis glutamine synthetase for drug discovery. Bioorg. Med. Chem. 2008, 16, 5501–5513.