Abstract
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.