Peng Xiangda, Zhang Yuebin, Li Yan, Liu QingLong, Chu Huiying, Zhang Dinglin, Li Guohui
Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics , Chinese Academy of Sciences , Dalian 116023 , P. R. China.
Chinese Academy of Science, University of Chinese Academy Sciences, Beijing 100049 , P. R. China.
J Chem Theory Comput. 2018 Mar 13;14(3):1216-1227. doi: 10.1021/acs.jctc.7b01211. Epub 2018 Feb 14.
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.
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，重加权过程中存在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，通过整合一系列具有不同加速参数的aMD子项，以同时提高采样效率并保持重加权精度。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，系统地将我们的IaMD方法与aMD进行比较。这些案例研究表明，在相同的加速水平和模拟时间下，IaMD在自由能分布重加权中的统计噪声远小于aMD。为了达到与IaMD相同的精度，aMD需要的模拟时间长1 - 3个数量级，这取决于模拟系统的复杂性和加速水平。在对快速折叠蛋白进行aMD模拟时使用高加速参数时，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，在丙氨酸二肽的案例中IaMD与集成回火采样（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。
