Simulating replica exchange simulations of protein folding with a kinetic network model
Simulating replica exchange simulations of protein folding with a kinetic network model
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DOI：
10.1073/pnas.0704418104
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发表时间：
2007-09-25
影响因子：
11.1
通讯作者：
Levy, Ronald M.
中科院分区：
文献类型：
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作者：
Zheng, Weihua;Andrec, Michael;Levy, Ronald M.
副本交换(RE)是一种用于加速自由能场景探索的广义系综模拟方法，它定义了计算生物物理学中的许多具有挑战性的问题，包括蛋白质折叠和结合。尽管温度RE(T-RE)是一种并行模拟技术，其实现相对简单，但T-RE系综中的动力学和平衡方法非常复杂；关于如何最好地利用T-RE来解决蛋白质折叠和结合问题，有很多需要学习的东西。我们构建了一个用于蛋白质折叠的RE研究的动力学网络模型，并使用这个简化的模型进行了“模拟模拟”，以分析构象动力学的基本温度依赖性和RE的基本参数(例如，复制数、RE速率和温度间距)如何相互作用来影响观察到的折叠转变的数量。当蛋白质折叠遵循反Arrhenius动力学时，我们观察到在感兴趣的低温下观察到的折叠转变次数的速度限制，这取决于高温下折叠和展开转变速率的调和平均值的最大值。这里显示的网络RE模型的结果建议了改进原子级RE模拟的方法，例如在执行RE研究之前使用“训练”模拟来探索原子级模型折叠的温度依赖性的某些方面。
Replica exchange (RE) is a generalized ensemble simulation method for accelerating the exploration of free-energy landscapes, which define many challenging problems in computational biophysics, including protein folding and binding. Although temperature RE (T-RE) is a parallel simulation technique whose implementation is relatively straightforward, kinetics and the approach to equilibrium in the T-RE ensemble are very complicated; there is much to learn about how to best employ T-RE to protein folding and binding problems. We have constructed a kinetic network model for RE studies of protein folding and used this reduced model to carry out "simulations of simulations" to analyze how the underlying temperature dependence of the conformational kinetics and the basic parameters of RE (e.g., the number of replicas, the RE rate, and the temperature spacing) all interact to affect the number of folding transitions observed. When protein folding follows anti-Arrhenius kinetics, we observe a speed limit for the number of folding transitions observed at the low temperature of interest, which depends on the maximum of the harmonic mean of the folding and unfolding transition rates at high temperature. The results shown here for the network RE model suggest ways to improve atomic-level RE simulations such as the use of "training" simulations to explore some aspects of the temperature dependence for folding of the atomic-level models before performing RE studies.