Charting a Path to Success in Virtual Screening.
Docking is commonly applied to drug design efforts, especially high-throughput virtual screenings of small molecules, to identify new compounds that bind to a given target. Despite great advances and successful applications in recent years, a number of issues remain unsolved. Most of the challenges and problems faced when running docking experiments are independent of the specific software used, and can be ascribed to either improper input preparation or to the simplified approaches applied to achieve high-throughput speed. Being aware of approximations and limitations of such methods is essential to prevent errors, deal with misleading results, and increase the success rate of virtual screening campaigns. In this review, best practices and most common issues of docking and virtual screening will be discussed, covering the journey from the design of the virtual experiment to the hit identification.
Molecular Graphics Laboratory, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. forli@scripps.edu.
Stefano
S
Forli
D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D057166:High-Throughput Screening Assays; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011506:Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011522:Protons; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry*; D012984:Software; D055672:Static Electricity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
D008024:Ligands; D011506:Proteins; D011522:Protons; D054852:Small Molecule Libraries
docking; drug design; molecular modeling; virtual screening