CORE-MD II: A fast, adaptive, and accurate enhanced sampling method.
CORE-MD II: A fast, adaptive, and accurate enhanced sampling method.
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DOI：
10.1063/5.0063664
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发表时间：
2021-09
期刊：
影响因子：
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通讯作者：
E. Peter;D. Manstein;J. Shea;A. Schug
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文献类型：
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作者：
E. Peter;D. Manstein;J. Shea;A. Schug
本文提出了一种快速自适应的相关引导增强采样方法（CORE-MD II）。CORE-MD II技术部分依赖于将整个路径划分为我们称为实例的短轨迹。每个实例内的采样通过自适应路径依赖元自适应模拟来加速。该方法的第二部分涉及在每个实例期间访问的不同状态之间的动力学蒙特卡罗（kMC）采样。通过将总模拟划分为短的非平衡模拟和kMC采样相结合，CORE-MD II方法能够在没有任何先验定义的反应途径和额外参数的情况下对蛋白质折叠进行采样。在验证模拟中，我们将CORE-MD II应用于dialanine肽和两种肽的折叠：TrpCage和TrpZip 2。在与长时间平衡分子动力学（MD），1 µs副本交换MD（REMD）和CORE-MD I模拟的比较中，我们发现CORE-MD II方法的收敛水平提高了8.8倍，而CORE-MD II方法的加速因子达到120倍。在TRpZip 2的CORE-MD II模拟中，我们观察到与REMD和CORE-MD I模拟相反的天然状态的形成。该方法广泛适用于MD模拟，并且不限于蛋白质折叠甚至生物分子的模拟，还适用于蛋白质聚集、蛋白质信号传导甚至材料科学模拟的模拟。
In this paper, we present a fast and adaptive correlation guided enhanced sampling method (CORE-MD II). The CORE-MD II technique relies, in part, on partitioning of the entire pathway into short trajectories that we refer to as instances. The sampling within each instance is accelerated by adaptive path-dependent metadynamics simulations. The second part of this approach involves kinetic Monte Carlo (kMC) sampling between the different states that have been accessed during each instance. Through the combination of the partition of the total simulation into short non-equilibrium simulations and the kMC sampling, the CORE-MD II method is capable of sampling protein folding without any a priori definitions of reaction pathways and additional parameters. In the validation simulations, we applied the CORE-MD II on the dialanine peptide and the folding of two peptides: TrpCage and TrpZip2. In a comparison with long time equilibrium Molecular Dynamics (MD), 1 µs replica exchange MD (REMD), and CORE-MD I simulations, we find that the level of convergence of the CORE-MD II method is improved by a factor of 8.8, while the CORE-MD II method reaches acceleration factors of ∼120. In the CORE-MD II simulation of TrpZip2, we observe the formation of the native state in contrast to the REMD and the CORE-MD I simulations. The method is broadly applicable for MD simulations and is not restricted to simulations of protein folding or even biomolecules but also applicable to simulations of protein aggregation, protein signaling, or even materials science simulations.