Ligand Binding and Release Investigated by Contact-Guided Iterative Multiple Independent Molecular Dynamics Simulations

Binding and releasing ligands are critical for the biological functions of many proteins, so it is important to determine these highly dynamic processes. Although there are experimental techniques to determine the structure of a protein-ligand complex, it only provides a static picture of the system. With the rapid increase of computing power and improved algorithms, molecular dynamics (MD) simulations have diverse of superiority in probing the binding and release process. However, it remains a great challenge to overcome the time and length scales when the system becomes large. This work presents an enhanced sampling tool for ligand binding and release, which is based on iterative multiple independent MD simulations guided by contacts formed between the ligand and the protein. From the simulation results on adenylate kinase, we observe the process of ligand binding and release while the conventional MD simulations at the same time scale cannot.