Pan Albert C, Sezer Deniz, Roux Benoît
Department of Biochemistry and Molecular Biology, Gordon Center of Integrative Science, University of Chicago, Chicago, Illinois, USA.
J Phys Chem B. 2008 Mar 20;112(11):3432-40. doi: 10.1021/jp0777059. Epub 2008 Feb 22.
An approach to find transition pathways in complex systems is presented. The method, which is related to the string method in collective variables of Maragliano et al. (J. Chem. Phys. 2006, 125, 024106), is conceptually simple and straightforward to implement. It consists of refining a putative transition path in the multidimensional space supported by a set of collective variables using the average dynamic drift of those variables. This drift is estimated on-the-fly via swarms of short unbiased trajectories started at different points along the path. Successive iterations of this algorithm, which can be naturally distributed over many computer nodes with negligible interprocessor communication, refine an initial trial path toward the most probable transition path (MPTP) between two stable basins. The method is first tested by determining the pathway for the C7eq to C7ax transition in an all-atom model of the alanine dipeptide in vacuum, which has been studied previously with the string method in collective variables. A transition path is found with a committor distribution peaked at 1/2 near the free energy maximum, in accord with previous results. Last, the method is applied to the allosteric conformational change in the nitrogen regulatory protein C (NtrC), represented here with a two-state elastic network model. Even though more than 550 collective variables are used to describe the conformational change, the path converges rapidly. Again, the committor distribution is found to be peaked around 1/2 near the free energy maximum between the two stable states, confirming that a genuine transition state has been localized in this complex multidimensional system.
本文提出了一种在复杂系统中寻找过渡路径的方法。该方法与Maragliano等人（《化学物理杂志》，2006年，第125卷，024106）在集体变量中的弦方法相关，概念简单且易于实现。它包括利用一组集体变量的平均动态漂移，在由这些变量支持的多维空间中优化一条假定的过渡路径。这种漂移通过沿着路径在不同点起始的大量短无偏轨迹即时估计。该算法的连续迭代可以自然地分布在许多计算机节点上，处理器间通信可忽略不计，从而将初始试验路径优化为两个稳定盆地之间最可能的过渡路径（MPTP）。该方法首先通过确定真空中丙氨酸二肽全原子模型中C7eq到C7ax转变的路径进行测试，此前已用集体变量中的弦方法对此进行过研究。发现一条过渡路径，其反应坐标分布在自由能最大值附近峰值为1/2，与先前结果一致。最后，该方法应用于氮调节蛋白C（NtrC）的变构构象变化，这里用两态弹性网络模型表示。尽管使用了超过550个集体变量来描述构象变化，但路径收敛迅速。同样，发现反应坐标分布在两个稳定状态之间自由能最大值附近峰值约为1/2，证实了在这个复杂的多维系统中已定位到一个真正的过渡态。
