Improved Reweighting of Accelerated Molecular Dynamics Simulations for Free Energy Calculation.
Improved Reweighting of Accelerated Molecular Dynamics Simulations for Free Energy Calculation.
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DOI：
10.1021/ct500090q
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发表时间：
2014-07-08
影响因子：
5.5
通讯作者：
McCammon, J. Andrew
中科院分区：
文献类型：
--
作者：
Miao, Yinglong;Sinko, William;Pierce, Levi;Bucher, Denis;Walker, Ross C.;McCammon, J. Andrew
加速分子动力学（aMD）模拟大大提高了传统分子动力学（cMD）采样生物分子构象的效率，但它们需要适当的重新加权的自由能计算。在这项工作中，我们系统地比较了不同的重加权算法，包括指数平均，麦克劳林系列，累积量扩展三个模型系统的准确性：丙氨酸二肽，chignolin，色氨酸笼。指数平均重新加权仅在升压电势的分布较窄（例如，范围≤ 20 kBT），如在丙氨酸二肽的二面体增强aMD模拟中发现的。在所研究系统的双助推aMD模拟中，指数平均通常导致高能量波动，这主要是由于玻尔兹曼重新加权因子由非常少的高助推潜力帧主导的事实。相比之下，基于麦克劳林级数展开（等价于一阶累积量展开）的重新加权极大地抑制了能量噪声，但通常给出不正确的能量最小值位置和能量势垒处的显著误差（102 - 3 kBT）。最后，使用累积量扩展到二阶的重新加权能够在PkBT的统计误差内恢复最准确的自由能分布，特别是当升压电势的分布表现出低非谐性时（即，近似高斯分布），并且应该具有广泛的适用性。用于aMD重新加权的Python脚本工具包“PyReweighting”免费发布于。
Accelerated molecular dynamics (aMD) simulations greatly improve the efficiency of conventional molecular dynamics (cMD) for sampling biomolecular conformations, but they require proper reweighting for free energy calculation. In this work, we systematically compare the accuracy of different reweighting algorithms including the exponential average, Maclaurin series, and cumulant expansion on three model systems: alanine dipeptide, chignolin, and Trp-cage. Exponential average reweighting can recover the original free energy profiles easily only when the distribution of the boost potential is narrow (e.g., the range ≤20kBT) as found in dihedral-boost aMD simulation of alanine dipeptide. In dual-boost aMD simulations of the studied systems, exponential average generally leads to high energetic fluctuations, largely due to the fact that the Boltzmann reweighting factors are dominated by a very few high boost potential frames. In comparison, reweighting based on Maclaurin series expansion (equivalent to cumulant expansion on the first order) greatly suppresses the energetic noise but often gives incorrect energy minimum positions and significant errors at the energy barriers (∼2–3kBT). Finally, reweighting using cumulant expansion to the second order is able to recover the most accurate free energy profiles within statistical errors of ∼kBT, particularly when the distribution of the boost potential exhibits low anharmonicity (i.e., near-Gaussian distribution), and should be of wide applicability. A toolkit of Python scripts for aMD reweighting “PyReweighting” is distributed free of charge at .
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影响因子：
5.5
作者：
Goetz, Andreas W.;Williamson, Mark J.;Xu, Dong;Poole, Duncan;Le Grand, Scott;Walker, Ross C.
通讯作者：
Walker, Ross C.
DOI：
10.1021/jz101462n
发表时间：
2011-02-03
期刊：
The journal of physical chemistry letters
影响因子：
--
作者：
Markwick PR;Pierce LC;Goodin DB;McCammon JA
通讯作者：
McCammon JA
DOI：
10.1039/c3cp53962h
发表时间：
2014-04-14
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Miao Y;Nichols SE;McCammon JA
通讯作者：
McCammon JA
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
2.4
作者：
Jarzynski, C
通讯作者：
Jarzynski, C