A steered molecular dynamics method with adaptive direction adjustments

In this paper, a new steered molecular dynamics (SMD) method with adjusting pulling direction is proposed to search an optimum trajectory of ligand dissociation. A multiobjective model and a searching technique based on information entropy with multi-population are developed to optimize the pulling direction. The improved method has been used to dissociate the substrate-bound complex structure of cytochrome P450 3A4-metyrapone. A more favorable dissociation pathway can be gained. The results show that the new pathway obtained by the proposed method has less dissociation time, smaller rupture force and lower energy barrier than that by the conventional SMD.