A steered molecular dynamics method with direction optimization and its applications on ligand molecule dissociation.
In this paper, a steered molecular dynamics method with pulling direction optimization is proposed to dissociate ligand molecule from receptor. A multi-population genetic algorithm based on the information entropy is developed to search the optimal pulling direction. By imposing an optimization phase in the conventional steered molecular dynamics simulation, a better substrate-exit channel for the buried active site can be found. The novel simulation method has been used to dissociate the substrate-bound complex structure of cytochrome P450 3A4-metyrapone. The results show that the new pathway obtained by the proposed method has advantages such as lower energy barrier, less dissociation time and shorter motion trajectory than that by the conventional steered molecular dynamics.
Liu
Xinli
X
Department of Engineering Mechanics, State Key Laboratory of Structural Analysis for Industrial Equipment, Dalian University of Technology, Dalian 116023, Liaoning, China.
Wang
Xicheng
X
Jiang
Huangliang
H
D003198:Computer Simulation; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D013997:Time Factors
D008024:Ligands; D006418:Heme; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human