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.
Yang
Kun
K
Department of Engineering Mechanics, State Key Laboratory of Structural Analysis for Industrial Equipment, Dalian University of Technology, Dalian 116024, China. yangkun@dlut.edu.cn
Liu
Xinli
X
Wang
Xicheng
X
Jiang
Hualiang
H
D000465:Algorithms; D003198:Computer Simulation; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry; D019277:Entropy; D004791:Enzyme Inhibitors / Q000737:chemistry; D008024:Ligands; D055595:Mechanical Phenomena; D008797:Metyrapone / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation
D004791:Enzyme Inhibitors; D008024:Ligands; D051544:Cytochrome P-450 CYP3A; D008797:Metyrapone