TY - JOUR T1 - Computational Methods in Drug Discovery JF - Pharmacological Reviews JO - Pharmacol Rev SP - 334 LP - 395 DO - 10.1124/pr.112.007336 VL - 66 IS - 1 AU - Gregory Sliwoski AU - Sandeepkumar Kothiwale AU - Jens Meiler AU - Edward W. Lowe, Jr. A2 - Barker, Eric L. Y1 - 2014/01/01 UR - http://pharmrev.aspetjournals.org/content/66/1/334.abstract N2 - 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. ER -