A novel multiscale scheme to accelerate atomistic simulations of bio-macromolecules by adaptively driving coarse-grained coordinates.
A novel multiscale scheme to accelerate atomistic simulations of bio-macromolecules by adaptively driving coarse-grained coordinates.
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DOI：
10.1063/1.5135309
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发表时间：
2020-03
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影响因子：
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通讯作者：
Kai Wu;Shun Xu;Biao Wan;P. Xiu;Xin Zhou
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文献类型：
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作者：
Kai Wu;Shun Xu;Biao Wan;P. Xiu;Xin Zhou
生物大分子的全原子分子动力学(MD)模拟可以得到相对准确的结果，但受到构象采样不足的限制。另一方面，粗粒度(CG)分子动力学模拟有效地加速了生物分子的构象变化，但失去了原子细节和准确性。在这里，我们提出了一种新的多尺度模拟方法，称为自适应驱动多尺度模拟(ADMS)-它通过自适应地在飞行中驱动虚拟CG原子来加速生物分子动力学，同时保持原子细节，并专注于原始系统的重要构象，而不相关的构象很少被采样。这里的“自适应驱动”是基于系统的短时平均响应(即原始系统的近似自由能面)，而不需要构造CG力场。作为例证，我们将ADMS应用于两个多肽(Deca-Alanine和Ace-GGPGGG-NME)和一个小蛋白(HP35)。模拟表明，ADMS不仅有效地捕捉生物分子的重要构象状态，驱动快速的州际转换，而且尽管它可能是部分可靠的蛋白质折叠途径，但也产生了可靠的折叠路径。值得注意的是，具有三个CG原子的HP35的∼100 ns显式溶剂ADMS轨迹实现了重复折叠和展开，并捕捉到了与398微米S标准全原子MD模拟相当的重要状态。
All-atom molecular dynamics (MD) simulations of bio-macromolecules can yield relatively accurate results while suffering from the limitation of insufficient conformational sampling. On the other hand, the coarse-grained (CG) MD simulations efficiently accelerate conformational changes in biomolecules but lose atomistic details and accuracy. Here, we propose a novel multiscale simulation method called the adaptively driving multiscale simulation (ADMS)-it efficiently accelerates biomolecular dynamics by adaptively driving virtual CG atoms on the fly while maintaining the atomistic details and focusing on important conformations of the original system with irrelevant conformations rarely sampled. Herein, the "adaptive driving" is based on the short-time-averaging response of the system (i.e., an approximate free energy surface of the original system), without requiring the construction of the CG force field. We apply the ADMS to two peptides (deca-alanine and Ace-GGPGGG-Nme) and one small protein (HP35) as illustrations. The simulations show that the ADMS not only efficiently captures important conformational states of biomolecules and drives fast interstate transitions but also yields, although it might be in part, reliable protein folding pathways. Remarkably, a ∼100-ns explicit-solvent ADMS trajectory of HP35 with three CG atoms realizes folding and unfolding repeatedly and captures the important states comparable to those from a 398-µs standard all-atom MD simulation.