Effect of query molecules on ligand-based virtual screening

Abstract

For ligand-based virtual screening (VS) using three-dimensional information of query molecules, it is thought that experimentally determined binding modes of query molecules provide better performance of selecting active compounds. Furthermore, using an ensemble of compounds similar to a query active compound contributed to giving better screening performance than using the single query compound when using two-dimensional molecular representations. In this study, we investigated the importance of conformations of query molecules and the degree of VS performance enhancement when using ensemble of queries with three-dimensional molecular representations. Our results indicate that conformations are not so important for ligand-based VS and using an ensemble of compounds similar to a query compound is a reasonable strategy for VS using three-dimensional molecular representations.