Overview of Computer-Aided Drug Discovery

William Jorgensen
Yale University

An overview of activities in the field will be provided covering lead discovery by docking, de novo design, lead optimization using free-energy methods, and prediction of pharmacological properties and toxicity. Current challenges and common mistakes will be discussed including undesirable substructures, frequent hitters in virtual screening, force-field accuracy, water placement in simulations, and patent awareness.

Background References:

1) Prediction of ‘drug-likeness’. Walters, W. P.; Murcko, M. A. Adv. Drug Del. Rev. 2002, 54, 255-271.

2) The Many Roles of Computation in Drug Discovery. Jorgensen, W. L., Science 2004, 303, 1813-1818.

3) Virtual ligand screening: strategies, perspectives and limitations. Klebe, G. Drug Disc. Today 2006, 11, 580-594.

4) Efficient Drug Lead Discovery and Optimization. Jorgensen, W. L. Acc. Chem. Res. 2009, 42, 724-733.

5) New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays. Baell, J. A.; Holloway, G. A. J. Med. Chem. 2010, 53, 2719-2740.

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