title: Computational methods in drug discovery.
abstract: Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature.
authors.affiliation: Jr., Center for Structural Biology, 465 21st Ave South, BIOSCI/MRBIII, Room 5144A, Nashville, TN 37232-8725. edward.w.lowe@vanderbilt.edu.
authors.forename: Gregory
authors.initials: G
authors.lastname: Sliwoski
authors.forename: Sandeepkumar
authors.initials: S
authors.lastname: Kothiwale
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
authors.forename: Edward W
authors.initials: EW
authors.lastname: Lowe
mesh_terms: D000818:Animals; D017076:Computer-Aided Design; D055808:Drug Discovery; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations