(How to) Profit from Molecular Dynamics-based Ensemble Docking

Abstract

Computational techniques have provided the field of drug discovery with enormous advances over the last decades. The development of methods covering dynamical aspects in protein–ligand binding is currently leading computer-aided drug design to new levels of complexity as well as accuracy. In this book chapter we focus on molecular docking to structural ensembles generated by molecular dynamics (MD) simulations. Does the incorporation of multiple receptor conformations allow pushing the borders for molecular docking or does it just lead to an artificial increase in false positive hit rates due to a broader conformational space of the receptor? We aim to identify guidelines for the best practice of molecular dynamics simulation-based ensemble docking from recent studies in the literature. Hence, we split the computational workflow for MD-based ensemble docking into the respective steps starting from protein structure and compound database to in silico hit lists. Thereby, we focus on the identification of successful strategies for virtual screening.