In silico screening of compound libraries using a consensus of orthogonal methodologies

Abstract

A number of diverse approaches for efficient screening of compound collections in silico are nowadays available, each with their own methodological background, successes and limitations. Implementation of such virtual screening methods has enabled an impressive acceleration in the search toward the most biologically relevant regions of chemical space and has greatly facilitated the discovery of novel biologically active molecules. It is noteworthy that the range of principles on which the available virtual screening methodologies are based is wide enough for several of these methods to be considered as orthogonal to a good extent. We hereby propose a simple and extensible protocol aiming at integrating the diverse information derived by such virtual screening methods in a consensus manner that can achieve an improvement of the hit rate obtained by individual use of those methods. The protocol can be performed in its basic version as described in this work, but it can also be extended manually by integrating a number of different screening tools and their case-specific variations to further increase the performance of virtual screening in prioritizing the most promising compounds for in vitro evaluations.