Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto Japan.
Biophys J. 2010 Apr 21;98(8):1649-57. doi: 10.1016/j.bpj.2009.12.4318.
Ligand migration processes inside myoglobin and protein dynamics coupled to the migration were theoretically investigated with molecular dynamics simulations. Based on a linear response theory, we identified protein motions coupled to the transient migration of ligand, carbon monoxide (CO), through channels. The result indicates that the coupled protein motions involve collective motions extended over the entire protein correlated with local gating motions at the channels. Protein motions, coupled to opening of a channel from the distal pocket to a neighboring xenon site, were found to share the collective motion with experimentally observed protein motions coupled to a doming motion of the heme Fe atom upon photodissociation of the ligand. Analysis based on generalized Langevin dynamics elucidated slow and diffusive features of the protein response motions. Remarkably small transmission coefficients for rates of the CO migrations through myoglobin were found, suggesting that the CO migration dynamics are characterized as motions governed by the protein dynamics involving the collective motions, rather than as thermally activated transitions across energy barriers of well-structured channels.
运用分子动力学模拟，从理论上研究了肌红蛋白内部配体迁移过程和与迁移相关的蛋白质动力学。基于线性响应理论，我们确定了与配体（一氧化碳，CO）通过通道的瞬态迁移相关的蛋白质运动。结果表明，耦合的蛋白质运动涉及跨越整个蛋白质的集体运动，与通道处的局部门控运动相关。发现与实验观察到的蛋白质运动相关的蛋白质运动，当配体光解时，与血红素 Fe 原子的穹顶运动相关联，与从远端口袋到邻近氙气位的通道开口耦合，这些运动与通道的结构能量障碍的热激活跃迁不同，而是与集体运动相关联。基于广义朗之万动力学的分析揭示了蛋白质响应运动的缓慢和扩散特征。发现通过肌红蛋白的 CO 迁移率的传输系数非常小，这表明 CO 迁移动力学的特点是由涉及集体运动的蛋白质动力学控制的运动，而不是由结构良好的通道的能量障碍的热激活跃迁控制的运动。
