Multiplexed-replica exchange molecular dynamics method for protein folding simulation
Multiplexed-replica exchange molecular dynamics method for protein folding simulation
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DOI：
10.1016/s0006-3495(03)74897-8
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发表时间：
2003-02-01
影响因子：
3.4
通讯作者：
Pande, VS
中科院分区：
文献类型：
--
作者：
Rhee, YM;Pande, VS
从蛋白质序列出发模拟蛋白质折叠热力学是计算生物学的一大挑战。在这里，我们提出了一种从蛋白质折叠的分子动力学模拟中计算正则分布的算法。该算法基于副本交换方法，通过交换在不同温度下模拟的非交互副本来克服动态捕获问题。我们的算法使用多路复制品，在每个温度下运行多个独立的分子动力学。还尝试了这些多路复制品之间的配置交换，使得该算法适用于大规模分布式计算(即，具有不同计算能力的处理器的高度异构性并行计算机)。我们通过模拟一个23个氨基酸的小蛋白的折叠热力学来演示该算法的增强采样。我们发现，与恒温分子动力学模拟相比，该方法具有更好的收敛性能，并且可以有效地扩展到大量的计算机处理器。事实上，这种增强的采样导致(据我们所知)从完全展开的状态开始对折叠结构进行采样的副本交换算法的第一个例子。
Simulating protein folding thermodynamics starting purely from a protein sequence is a grand challenge of computational biology. Here, we present an algorithm to calculate a canonical distribution from molecular dynamics simulation of protein folding. This algorithm is based on the replica exchange method where the kinetic trapping problem is overcome by exchanging noninteracting replicas simulated at different temperatures. Our algorithm uses multiplexed-replicas with a number of independent molecular dynamics runs at each temperature. Exchanges of configurations between these multiplexed-replicas are also tried, rendering the algorithm applicable to large-scale distributed computing (i.e., highly heterogeneous parallel computers with processors having different computational power). We demonstrate the enhanced sampling of this algorithm by simulating the folding thermodynamics of a 23 amino acid miniprotein. We show that better convergence is achieved compared to constant temperature molecular dynamics simulation, with an efficient scaling to large number of computer processors. Indeed, this enhanced sampling results in (to our knowledge) the first example of a replica exchange algorithm that samples a folded structure starting from a completely unfolded state.