Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 303 (5665): 1813-1818

Copyright © 2004 by the American Association for the Advancement of Science

The Many Roles of Computation in Drug Discovery

William L. Jorgensen

Abstract: An overview is given on the diverse uses of computational chemistry in drug discovery. Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for determining protein-ligand binding.

Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.

E-mail: william.jorgensen{at}

Computational Methods in Drug Discovery.
G. Sliwoski, S. Kothiwale, J. Meiler, and E. W. Lowe Jr. (2013)
Pharmacol. Rev. 66, 334-395
   Abstract »    Full Text »    PDF »
Modern bioinformatics meets traditional Chinese medicine.
P. Gu and H. Chen (2013)
Brief Bioinform
   Abstract »    Full Text »    PDF »
Funnel metadynamics as accurate binding free-energy method.
V. Limongelli, M. Bonomi, and M. Parrinello (2013)
PNAS 110, 6358-6363
   Abstract »    Full Text »    PDF »
Bioinformatics opportunities for identification and study of medicinal plants.
V. Sharma and I. N. Sarkar (2013)
Brief Bioinform 14, 238-250
   Abstract »    Full Text »    PDF »
Overcoming mutation-based resistance to antiandrogens with rational drug design.
M. D. Balbas, M. J. Evans, D. J. Hosfield, J. Wongvipat, V. K. Arora, P. A. Watson, Y. Chen, G. L. Greene, Y. Shen, and C. L. Sawyers (2013)
eLife Sci 2, e00499
   Abstract »    Full Text »    PDF »
Adaptation of Human Parainfluenza Virus to Airway Epithelium Reveals Fusion Properties Required for Growth in Host Tissue.
S. G. Palmer, M. Porotto, L. M. Palermo, L. F. Cunha, O. Greengard, and A. Moscona (2012)
mBio 3, e00137-12
   Abstract »    Full Text »    PDF »
Identification of a Small Molecule That Modulates Platelet Glycoprotein Ib-von Willebrand Factor Interaction.
K. Broos, M. Trekels, R. A. Jose, J. Demeulemeester, A. Vandenbulcke, N. Vandeputte, T. Venken, B. Egle, W. M. De Borggraeve, H. Deckmyn, et al. (2012)
J. Biol. Chem. 287, 9461-9472
   Abstract »    Full Text »    PDF »
Determination of Noncovalent Docking by Infrared Spectroscopy of Cold Gas-Phase Complexes.
E. Garand, M. Z. Kamrath, P. A. Jordan, A. B. Wolk, C. M. Leavitt, A. B. McCoy, S. J. Miller, and M. A. Johnson (2012)
Science 335, 694-698
   Abstract »    Full Text »    PDF »
Flexibility and binding affinity in protein-ligand, protein-protein and multi-component protein interactions: limitations of current computational approaches.
P. Tuffery and P. Derreumaux (2012)
J R Soc Interface 9, 20-33
   Abstract »    Full Text »    PDF »
MDpocket: open-source cavity detection and characterization on molecular dynamics trajectories.
P. Schmidtke, A. Bidon-Chanal, F. J. Luque, and X. Barril (2011)
Bioinformatics 27, 3276-3285
   Abstract »    Full Text »    PDF »
Ligand-receptor Interaction between Triterpenoids and the 11{beta}-Hydroxysteroid dehydrogenase type 2 (11{beta}HSD2) Enzyme Predicts Their Toxic Effects against Tumorigenic r/m HM-SFME-1 Cells.
H. Yamaguchi, T. Yu, T. Noshita, Y. Kidachi, K. Kamiie, K. Yoshida, T. Akitaya, H. Umetsu, and K. Ryoyama (2011)
J. Biol. Chem. 286, 36888-36897
   Abstract »    Full Text »    PDF »
SwissDock, a protein-small molecule docking web service based on EADock DSS.
A. Grosdidier, V. Zoete, and O. Michielin (2011)
Nucleic Acids Res. 39, W270-W277
   Abstract »    Full Text »    PDF »
Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations.
I. Buch, T. Giorgino, and G. De Fabritiis (2011)
PNAS 108, 10184-10189
   Abstract »    Full Text »    PDF »
Using Open Source Computational Tools for Predicting Human Metabolic Stability and Additional Absorption, Distribution, Metabolism, Excretion, and Toxicity Properties.
R. R. Gupta, E. M. Gifford, T. Liston, C. L. Waller, M. Hohman, B. A. Bunin, and S. Ekins (2010)
Drug Metab. Dispos. 38, 2083-2090
   Abstract »    Full Text »    PDF »
Molecular Dynamics Simulations Show That Conformational Selection Governs the Binding Preferences of Imatinib for Several Tyrosine Kinases.
A. Aleksandrov and T. Simonson (2010)
J. Biol. Chem. 285, 13807-13815
   Abstract »    Full Text »    PDF »
Binding Investigation of Integrin {alpha}v{beta}3 With Its Inhibitors by SPR Technology and Molecular Docking Simulation.
Y. Liu, Y. Pan, and Y. Xu (2010)
J Biomol Screen 15, 131-137
   Abstract »    Full Text »    PDF »
Dehydrogenation of the Indoline-Containing Drug 4-Chloro-N-(2-methyl-1-indolinyl)-3-sulfamoylbenzamide (Indapamide) by CYP3A4: Correlation with in Silico Predictions.
H. Sun, C. Moore, P. M. Dansette, S. Kumar, J. R. Halpert, and G. S. Yost (2009)
Drug Metab. Dispos. 37, 672-684
   Abstract »    Full Text »    PDF »
Introduction. Biomolecular simulation.
A. J Mulholland (2008)
J R Soc Interface 5, 169-172
   Abstract »    Full Text »    PDF »
Calculation of protein-ligand binding free energy by using a polarizable potential.
D. Jiao, P. A. Golubkov, T. A. Darden, and P. Ren (2008)
PNAS 105, 6290-6295
   Abstract »    Full Text »    PDF »
Potent and selective inhibitors of Staphylococcus epidermidis tryptophanyl-tRNA synthetase.
Y. Wu, K. Yu, B. Xu, L. Chen, X. Chen, J. Mao, A. Danchin, X. Shen, D. Qu, and H. Jiang (2007)
J. Antimicrob. Chemother. 60, 502-509
   Abstract »    Full Text »    PDF »
Structurally Unique Inhibitors of Human Mitogen-Activated Protein Kinase Phosphatase-1 Identified in a Pyrrole Carboxamide Library.
J. S. Lazo, J. J. Skoko, S. Werner, B. Mitasev, A. Bakan, F. Koizumi, A. Yellow-Duke, I. Bahar, and K. M. Brummond (2007)
J. Pharmacol. Exp. Ther. 322, 940-947
   Abstract »    Full Text »    PDF »
Crystal Structures of Two Bacterial 3-Hydroxy-3-methylglutaryl-CoA Lyases Suggest a Common Catalytic Mechanism among a Family of TIM Barrel Metalloenzymes Cleaving Carbon-Carbon Bonds.
F. Forouhar, M. Hussain, R. Farid, J. Benach, M. Abashidze, W. C. Edstrom, S. M. Vorobiev, R. Xiao, T. B. Acton, Z. Fu, et al. (2006)
J. Biol. Chem. 281, 7533-7545
   Abstract »    Full Text »    PDF »
Two Domains That Control Prefusion Stability and Transport Competence of the Measles Virus Fusion Protein.
J. Doyle, A. Prussia, L. K. White, A. Sun, D. C. Liotta, J. P. Snyder, R. W. Compans, and R. K. Plemper (2006)
J. Virol. 80, 1524-1536
   Abstract »    Full Text »    PDF »
Virtual Ligand Screening against Escherichia coli Dihydrofolate Reductase: Improving Docking Enrichment Using Physics-Based Methods.
K. Bernacki, C. Kalyanaraman, and M. P. Jacobson (2005)
J Biomol Screen 10, 675-681
   Abstract »    PDF »
Grid-based steered thermodynamic integration accelerates the calculation of binding free energies.
P. W Fowler, S. Jha, and P. V Coveney (2005)
Phil Trans R Soc A 363, 1999-2015
   Abstract »    Full Text »    PDF »
MEDock: a web server for efficient prediction of ligand binding sites based on a novel optimization algorithm.
D. T.-H. Chang, Y.-J. Oyang, and J.-H. Lin (2005)
Nucleic Acids Res. 33, W233-W238
   Abstract »    Full Text »    PDF »
Ofloxacin-like Antibiotics Inhibit Pneumococcal Cell Wall-degrading Virulence Factors.
C. Fernandez-Tornero, E. Garcia, B. de Pascual-Teresa, R. Lopez, G. Gimenez-Gallego, and A. Romero (2005)
J. Biol. Chem. 280, 19948-19957
   Abstract »    Full Text »    PDF »
Interaction between Cardiac Calsequestrin and Drugs with Known Cardiotoxicity.
I. Y. Park, E. J. Kim, H. Park, K. Fields, A. K. Dunker, and C. Kang (2005)
Mol. Pharmacol. 67, 97-104
   Abstract »    Full Text »    PDF »
Accelerating drug discovery: Although the evolution of '-omics' methodologies is still in its infancy, both the pharmaceutical industry and patients could benefit from their implementation in the drug development process.
S. Kraljevic, P. J. Stambrook, and K. Pavelic (2004)
EMBO Rep. 5, 837-842
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882