Demonstrating an Order-of-Magnitude Sampling Enhancement in Molecular Dynamics Simulations of Complex Protein Systems
Demonstrating an Order-of-Magnitude Sampling Enhancement in Molecular Dynamics Simulations of Complex Protein Systems
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DOI：
10.1021/acs.jctc.5b00913
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发表时间：
2016-03-01
影响因子：
5.5
通讯作者：
Shaw, David E.
中科院分区：
文献类型：
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作者：
Pan, Albert C.;Weinreich, Thomas M.;Shaw, David E.
分子动力学（MD）模拟可以描述蛋白质运动的原子细节，但蛋白质构象状态之间的转换有时发生在时间尺度上，这是不可行的或非常昂贵的直接模拟达到。增强的采样方法，其目的是增加MD模拟的采样效率，因此被广泛采用。然而，这种方法的有效性，当应用于复杂的生物系统，如蛋白质，一直难以建立，因为即使增强采样模拟这样的系统通常不达到时间尺度，在收敛是广泛的，足以可靠地量化采样效率。在这里，我们获得了充分收敛的模拟三种蛋白质，以评估模拟回火的性能，一个成员的广泛使用的一类增强的采样方法，使用升高的温度来加速采样。模拟回火模拟与个人长度高达100，我们进行了比较（以前公布的）传统的MD模拟与个人长度高达1毫秒。与两种蛋白质，BPTI和泛素，我们评估了效率的采样构象状态附近的天然状态，第三，绒毛头部，我们研究了折叠和展开的速度。我们的比较表明，模拟回火可以始终实现一个数量级或更多的相对于传统的MD大幅采样加速。
Molecular dynamics (MD) simulations can describe protein motions in atomic detail, but transitions between protein conformational states sometimes take place on time scales that are infeasible or very expensive to reach by direct simulation. Enhanced sampling methods, the aim of which is to increase the sampling efficiency of MD simulations, have thus been extensively employed. The effectiveness of such methods when applied to complex biological systems like proteins, however, has been difficult to establish because even enhanced sampling simulations of such systems do not typically reach time scales at which convergence is extensive enough to reliably quantify sampling efficiency. Here, we obtain sufficiently converged simulations of three proteins to evaluate the performance of simulated tempering, a member of a widely used class of enhanced sampling methods that use elevated temperature to accelerate sampling. Simulated tempering simulations with individual lengths of up to 100,us were compared to (previously published) conventional MD simulations with individual lengths of up to 1 ms. With two proteins, BPTI and ubiquitin, we evaluated the efficiency of sampling of conformational states near the native state, and for the third, the villin headpiece, we examined the rate of folding and unfolding. Our comparisons demonstrate that simulated tempering can consistently achieve a substantial sampling speedup of an order of magnitude or more relative to conventional MD.