Ligand Docking and Structure-based Virtual Screening in Drug Discovery

CAVASOTTO, CLAUDIO N.; ORRY, ANDREW J.

Current Topics in Medicinal Chemistry

BENTHAM SCIENCE PUBL LTD

Año: 2007 vol. 7 p. 1006 - 1014

1568-0266

Ligand-docking-based methods are starting to play a critical role in lead discovery and optimization, thus resulting in new ‘drug-candidates’. They offer the possibility to go beyond the pool of existing active compounds, and thus find novel chemotypes. A brief tutorial on ligand docking and structure-based virtual screening is presented highlighting current problems and limitations, together with the most recent methodological and algorithmic developments in the field. Recent successful applications of docking-based tools for hit discovery, lead optimization and target-biased library design are also presented. Special consideration is devoted to ongoing efforts to account for protein flexibility in structure-based virtual screening.