A Steered Molecular Dynamics Method for Receptor-Ligand Unbinding Based on Genetic Algorithm

Steered molecular dynamics (SMD) method provides a new tool to investigate the structure-activity relationship, but its application is restricted severely when the real dissociation pathway is crooked. In this paper, a self-adaptive SMD method is designed for protein-ligand and protein-protein unbinding. During the unbinding process, the pulling direction varies automatically with a specified genetic algorithm to find the pathway which can be passed through with minimum force, so the rupture force of the unbinding process can be minimized and a rational dissociation pathway can be found the receptor-ligand complex. To evaluate the efficiency of the proposed method, several representative protein-ligand complexes and protein-protein complexes are simulated to pull the ligands away from the receptors. Compared with the conventional SMD, the new SMD scheme gains different dissociation pathways, and these new pathways generally have smaller rupture force and lower energy barrier.