Pseudoreceptor models in drug design: bridging ligand- and receptor-based virtual screening

Abstract

Rational drug design is based on explicit or implicit structure-activity relationship models. Typically, receptor-based or ligand-based strategies are pursued, depending on the information available about known ligands and the receptor structure. Pseudoreceptor models combine the advantages of these two strategies and represent a unifying concept for both receptor mapping and ligand matching. They can provide an entry point for structure-based modelling in drug discovery projects that lack a high-resolution structure of the target. Here, we review the field of pseudoreceptor modelling techniques along with recent hit and lead finding applications, and critically discuss prerequisites, advantages and limitations of the various approaches.