Ranking poses in structure-based lead discovery and optimization: current trends in scoring function development

Abstract

The ability to accurately predict the potency of ligand binding to its intended target prior to synthesis is of significant value in the drug-discovery paradigm. The protocols designed to this end follow a two-step process. First, ligands are docked into the active site of interest, and then the resulting interactions at the target are scored. Scoring functions form the key component in this process, providing a quantitative measure of fit quality. There is an abundance of new research in the field of scoring function design, from incorporation of novel descriptors (derived from first principles or empirical analysis) to function redesign based on improved data set handling. This article provides a brief overview on the state-of-the-art developments in the field, with particular reference to their performance in relation to expected outcomes.