Ligand docking and virtual screening in structure-based drug discovery

CAVASOTTO, CLAUDIO N.

Zaragoza

Conferencia; BIFI 2006 - II International Conference: From Physics to Biology: the interface between experiment and computation; 2006

Asthe number of high-resolution three-dimensional protein and nucleic acid structurescontinues to grow, ligand docking-based virtual screening ofchemical libraries to a receptor are playing a critical role in the drugdiscovery process by identifying new ?drug-candidates?. The capability tocorrectly predict ligand-protein interaction is fundamental to any accuratedocking algorithm and the necessary starting point for any reliable virtualscreening protocol. Furthermore, explicit considerationof receptor flexibility in computational ligand docking is emerging in manycases as crucial for an accurate prediction of the orientation and interactionsof ligands within the binding pocket. The combination of ligand docking with afast scoring algorithm that can account for the thermodynamics of binding, anddiscriminate between potential active/inactive compounds, can greatly reducedthe number of compounds to be tested experimentally, while predicting adetailed structure of hits bound to the receptor useful enough to help thesynthetic elaboration of leads.