Huber G A, Kim S
Department of Chemical Engineering, University of Wisconsin-Madison 53706, USA.
Biophys J. 1996 Jan;70(1):97-110. doi: 10.1016/S0006-3495(96)79552-8.
A new method, weighted-ensemble Brownian dynamics, is proposed for the simulation of protein-association reactions and other events whose frequencies of outcomes are constricted by free energy barriers. The method features a weighted ensemble of trajectories in configuration space with energy levels dictating the proper correspondence between "particles" and probability. Instead of waiting a very long time for an unlikely event to occur, the probability packets are split, and small packets of probability are allowed to diffuse almost immediately into regions of configuration space that are less likely to be sampled. The method has been applied to the Northrup and Erickson (1992) model of docking-type diffusion-limited reactions and yields reaction rate constants in agreement with those obtained by direct Brownian simulation, but at a fraction of the CPU time (10(-4) to 10(-3), depending on the model). Because the method is essentially a variant of standard Brownian dynamics algorithms, it is anticipated that weighted-ensemble Brownian dynamics, in conjunction with biophysical force models, can be applied to a large class of association reactions of interest to the biophysics community.
提出了一种新方法——加权系综布朗动力学，用于模拟蛋白质结合反应以及其他结果频率受自由能垒限制的事件。该方法的特点是在构型空间中采用加权轨迹系综，其能级决定了“粒子”与概率之间的正确对应关系。不是等待很长时间让不太可能发生的事件出现，而是将概率包进行分割，使小概率包几乎能立即扩散到构型空间中不太可能被采样到的区域。该方法已应用于Northrup和Erickson（1992年）的对接型扩散限制反应模型，并得到了与直接布朗模拟相符的反应速率常数，但所需的CPU时间仅为其一小部分（取决于模型，为10^(-4)到10^(-3)）。由于该方法本质上是标准布朗动力学算法的一种变体，预计加权系综布朗动力学与生物物理力模型相结合，可应用于生物物理学界感兴趣的一大类结合反应。
