Steered Molecular Dynamics Simulation in Rational Drug Design

Conventional de novo drug design is time consuming, laborious, and resource intensive. In recent years, emerging in silico approaches have been proven to be critical to accelerate the process of bringing drugs to market. Molecular dynamics (MD) simulations of single molecule and molecular complexes have been commonly applied to achieve accurate binding modes and binding energies of drug-receptor interactions. A derivative of MD, namely, steered molecular dynamics (SMD), has been demonstrated as a promising tool for rational drug design. In this paper, we review various studies over the last 20 years using SMD simulations, thus paving the way to determine the relationship between protein structure and function. In addition, the paper highlights the use of SMD simulation for in silico drug design. We also aim to establish an understanding on the key interactions which play a crucial role in the stabilization of peptide–ligand interfaces, the binding and unbinding mechanism of the ligand–protein complex, the mechanism of ligand translocating via membrane, and the ranking of different ligands on receptors as therapeutic candidates.