Computational methods in drug discovery.

Sliwoski G, Kothiwale S, Meiler J, Lowe EW
Pharmacol Rev. 2014 66 (1): 334-95

PMID: 24381236 · PMCID: PMC3880464 · DOI:10.1124/pr.112.007336

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.

MeSH Terms (9)

Animals Computer-Aided Design Drug-Related Side Effects and Adverse Reactions Drug Discovery Humans Ligands Molecular Structure Pharmaceutical Preparations Pharmacokinetics

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