Integrating Multiple Accelerated Molecular Dynamics To Improve Accuracy of Free Energy Calculations
Integrating Multiple Accelerated Molecular Dynamics To Improve Accuracy of Free Energy Calculations
复制标题
集成多个加速分子动力学以提高自由能计算的准确性
DOI：
10.1021/acs.jctc.7b01211
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发表时间：
2018
影响因子：
5.5
通讯作者：
Li Guohui
中科院分区：
文献类型：
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作者：
Peng Xiangda;Zhang Yuebin;Li Yan;Liu QingLong;Chu Huiying;Zhang Dinglin;Li Guohui
加速分子动力学（aMD）是一种很有前景的增强采样方法，用于探索生物分子的构象空间。然而，重新加权中的大量统计噪声限制了其恢复原始自由能分布的准确性。在这项工作中，我们提出了一种集成加速分子动力学（IaMD）方法，通过集成一系列具有不同加速参数的aMD子项来提高采样效率并同时保持重新加权精度。我们使用丙氨酸二肽和三种快速折叠蛋白（Chignolin、Trp-cage 和 Villin Headpiece）作为测试对象，系统地比较我们的 IaMD 方法和 aMD。这些案例研究表明，在相同的加速度和模拟时间水平下，IaMD 在自由能剖面重新加权中的统计噪声远小于 aMD。为了达到与 IaMD 相同的精度，aMD 需要比 IaMD 长 1-3 个数量级的仿真时间，具体取决于仿真系统的复杂性和加速水平。当在快速折叠蛋白质的 aMD 模拟中使用高加速参数时，我们的方法在控制由低能构象消失引起的系统误差方面也优于 aMD。此外，在丙氨酸二肽情况下，IaMD 与集成调温采样（ITS）的性能比较表明，IaMD 具有更好的控制采样势能区域的能力。
Accelerated Molecular Dynamics (aMD) is a promising enhanced sampling method to explore the conformational space of biomolecules. However, the large statistical noise in reweighting limits its accuracy to recover the original free energy profile. In this work, we propose an Integrated accelerated Molecule Dynamics (IaMD) method by integrating a series of aMD subterms with different acceleration parameters to improve the sampling efficiency and maintain the reweighting accuracy simultaneously. We use Alanine Dipeptide and three fast-folded proteins (Chignolin, Trp-cage, and Villin Headpiece) as the test objects to compare our IaMD method with aMD systematically. These case studies indicate that the statistical noise of IaMD in reweighting for free energy profiles is much smaller than that of aMD at the same level of acceleration and simulation time. To achieve the same accuracy as IaMD, aMD requires 1–3 orders of magnitude longer simulation time, depending on the complexity of the simulated system and the level of acceleration. Our method also outperforms aMD in controlling systematic error caused by the disappearance of the low-energy conformations when high acceleration parameters are used in aMD simulations for fast-folded proteins. Furthermore, the performance comparison between IaMD and the Integrated Tempering Sampling (ITS) in the case of Alanine Dipeptide demonstrates that IaMD possesses a better ability to control the potential energy region of sampling.