Docking and scoring in virtual screening for drug discovery: methods and applications.
Computational approaches that 'dock' small molecules into the structures of macromolecular targets and 'score' their potential complementarity to binding sites are widely used in hit identification and lead optimization. Indeed, there are now a number of drugs whose development was heavily influenced by or based on structure-based design and screening strategies, such as HIV protease inhibitors. Nevertheless, there remain significant challenges in the application of these approaches, in particular in relation to current scoring schemes. Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches.
Kitchen
Douglas B
DB
Department of Computer-Aided Drug Discovery, Albany Molecular Research, Inc., 21 Corporate Circle, Albany, New York 12212-5098, USA.
Decornez
Hélène
H
Furr
John R
JR
Bajorath
Jürgen
J
D001665:Binding Sites; D019295:Computational Biology / Q000379:methods / Q000639:trends; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship
D008024:Ligands