Rational Prediction with Molecular Dynamics for Hit Identification

Abstract

A review. Although the motions of proteins are fundamental for their function, for pragmatic reasons, the consideration of protein elasticity has traditionally been neglected in drug discovery and design. This review details protein motion, its relevance to biomol. interactions and how it can be sampled using mol. dynamics simulations. Within this context, two major areas of research in structure-based prediction that can benefit from considering protein flexibility, binding site detection and mol. docking, are discussed. Basic classification metrics and statistical anal. techniques, which can facilitate performance anal., are also reviewed. With hardware and software advances, mol. dynamics in combination with traditional structure-based prediction methods can potentially reduce the time and costs involved in the hit identification pipeline. [on SciFinder(R)]