Liu Xinli, Wang Xicheng, Jiang Huangliang
Department of Engineering Mechanics, State Key Laboratory of Structural Analysis for Industrial Equipment, Dalian University of Technology, Dalian 116023, Liaoning, China.
J Biochem Biophys Methods. 2008 Apr 24;70(6):857-64. doi: 10.1016/j.jbbm.2007.10.006. Epub 2007 Oct 24.
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.
