Computational Methods in Drug Discovery
| Autor: | Edward W. Lowe, Sandeepkumar Kothiwale, Jens Meiler, Gregory Sliwoski |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Pharmacology
Drug-Related Side Effects and Adverse Reactions Molecular Structure Drug discovery Chemistry Ligand Drug design Computational biology Ligands Combinatorial chemistry Small molecule ComputingMethodologies_PATTERNRECOGNITION Pharmaceutical Preparations Docking (molecular) Molecular descriptor Drug Discovery Animals Computer-Aided Design Humans Molecular Medicine Pharmacokinetics Homology modeling Pharmacophore Review Articles |
| Zdroj: | Pharmacological Reviews. 66:334-395 |
| ISSN: | 1521-0081 0031-6997 |
| DOI: | 10.1124/pr.112.007336 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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