How to optimize shape-based virtual screening: choosing the right query and including chemical information.
Shape-based molecular similarity approaches have been established as important and popular virtual screening techniques. Recent applications have shown successful screening campaigns using different parameters and query selection. It is common sense that pure volume overlap scoring (or "shape-based screening") under-represents chemical or pharmacophoric information of a molecule. Using the "Directory of Useful Decoys" (DUD) as a benchmark set, we systematically evaluate how (i) the choice of query conformations, (ii) the selection of the active compound to be used as a query structure, and (iii) the inclusion of chemical information (i.e., the pharmacophoric properties of the query molecule) affect screening performance. Varying these parameters bears remarkable potential for improvements and delivers the best screening performance reported using these tools so far. From these insights, guidelines on how to reach optimum performance during virtual screening are developed.
Kirchmair
Johannes
J
Department of Pharmaceutical Chemistry, Faculty of Chemistry and Pharmacy and Center for Molecular Biosciences (CMBI), University of Innsbruck, Innrain 52, A-6020 Innsbruck, Austria.
Distinto
Simona
S
Markt
Patrick
P
Schuster
Daniela
D
Spitzer
Gudrun M
GM
Liedl
Klaus R
KR
Wolber
Gerhard
G
D000991:Antithrombins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003201:Computers; D012984:Software
D000991:Antithrombins