Integrating virtual screening in lead discovery.
Target- and ligand-based virtual screening have emerged as resource-saving techniques that have been successfully applied to identify novel chemotypes in biologically active molecules. Eight confirmed virtual screening hits have recently been described and are discussed in this review, with focus on the workflow. These are then evaluated in the light of pharmacokinetics prediction (e.g. Caco-2 permeability, cytochrome P450 inhibition and hERG binding). We anticipate problems for five of these hits (e.g. cardiac toxicity), which warrant further experiments. Future challenges include dynamic tautomer/protonation treatment for both ligands and targets and improved pre- and post- virtual screening filters.
Oprea
Tudor I
TI
Division of Biocomputing, University of New Mexico School of Medicine, MSC 08 4560, 1 University of New Mexico, Albuquerque, New Mexico 87131-0001, USA. toprea@salud.unm.edu
Matter
Hans
H
D000818:Animals; D017076:Computer-Aided Design; D016208:Databases, Factual; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D008024:Ligands