采用分子动力学模拟方法评价人类VDAC通道蛋白晶体结构的生物活性

Assessing the Credibility of VDAC Structure with Molecular Dynamics Simulation Approach

为研究电压依赖阴离子选择性通道(VDAC)分子的调控机制,在有无电场存在情况下,对Ⅰ型人类VDAC分子(hVDAC1)分别进行了分子动力学模拟研究.结果表明,外加电场的有无与方向变化对hVDAC1分子的运动模式和离子通过过程影响不明显,hVDAC1分子仍然保持以N端α螺旋在β桶内横向运动为主的运动模式.综合模拟结果和相关的实验结果,推测hVDAC1晶体结构不是其发挥生理功能的结构状态.

Voltage dependent anion-selective channel（VDAC） is a vital protein family.This protein family is located in outer membrane of mitochondria.It is responsible for the trafficking of metabolites between cytosol and the intermembrane space of mitochondria.In order to cast light on understanding the regulation mechanism of VDAC molecule,we performed molecular dynamics simulations on human VDAC I（hVDAC1） molecule with or without additional electric field.However,the results show little effect of electric field on hVDAC1＇s essential motion and ion permeability.The dominant motion mode is still the horizontal movement of N-terminal α-helix in the β-barrel of hVDAC1.Considering published experiment results and the debate on the credibility of published 3D structure of VDAC,we speculate that the published VDAC structure may not be the {native} structure of in vivo VDAC molecules.