Hit Identification and Optimization in Virtual Screening: Practical Recommendations Based on a Critical Literature Analysis

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2013 May 22

PMID 23688234

Citations 105

Authors

Tian Zhu

Shuyi Cao

Pin-Chih Su

Ram Patel

Darshan Shah

Heta B Chokshi

Richard Szukala

Michael E Johnson

Kirk E Hevener

Affiliations

Soon will be listed here.

Abstract

A critical analysis of virtual screening results published between 2007 and 2011 was performed. The activity of reported hit compounds from over 400 studies was compared to their hit identification criteria. Hit rates and ligand efficiencies were calculated to assist in these analyses, and the results were compared with factors such as the size of the virtual library and the number of compounds tested. A series of promiscuity, druglike, and ADMET filters were applied to the reported hits to assess the quality of compounds reported, and a careful analysis of a subset of the studies that presented hit optimization was performed. These data allowed us to make several practical recommendations with respect to selection of compounds for experimental testing, definition of hit identification criteria, and general virtual screening hit criteria to allow for realistic hit optimization. A key recommendation is the use of size-targeted ligand efficiency values as hit identification criteria.

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