Diffusive reaction dynamics on invariant free energy profiles
Diffusive reaction dynamics on invariant free energy profiles
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DOI：
10.1073/pnas.0800228105
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发表时间：
2008-09-16
影响因子：
11.1
通讯作者：
Karplus, Martin
中科院分区：
文献类型：
--
作者：
Krivov, Sergei V.;Karplus, Martin
在蛋白质折叠和其他复杂反应的分析中，熵起着重要作用的一个基本问题是从实验测量或计算机模拟中确定活化自由能。本文展示了如何将从平衡分子动力学模拟获得的基于最小切割的自由能分布（F-C）与传统的基于直方图的自由能分布（F-H）结合起来，以提取F-C上的坐标相关扩散系数（即，该方法确定自由能和沿着适当反应坐标的扩散指前因子）。的F-C，在对比的F-H，示出相对于反应坐标的任意变换是不变的，这使得可能的配置空间的分区成盆在一个不变的方式。一个“自然坐标”，其中F-H和F-C不同的乘法常数（常数扩散系数），被引入。该方法说明了一个模型的一维系统，丙氨酸二肽，和双β-发夹miniprotein的折叠反应。它示出了如何的结果可以用来测试是否推定的反应坐标是一个很好的反应坐标。
A fundamental problem in the analysis of protein folding and other complex reactions in which the entropy plays an important role is the determination of the activation free energy from experimental measurements or computer simulations. This article shows how to combine minimum-cut-based free energy profiles (F-C), obtained from equilibrium molecular dynamics simulations, with conventional histogram-based free energy profiles (F-H) to extract the coordinate-dependent diffusion coefficient on the F-C (i.e., the method determines free energies and a diffusive preexponential factor along an appropriate reaction coordinate). The F-C, in contrast to the F-H, is shown to be invariant with respect to arbitrary transformations of the reaction coordinate, which makes possible partition of configuration space into basins in an invariant way. A "natural coordinate," for which F-H and F-C differ by a multiplicative constant (constant diffusion coefficient), is introduced. The approach is illustrated by a model one-dimensional system, the alanine dipeptide, and the folding reaction of a double beta-hairpin miniprotein. It is shown how the results can be used to test whether the putative reaction coordinate is a good reaction coordinate.