论文标题

GA引导的MD-VCMD:一种基于遗传叠加的方法,用于多维虚拟系统耦合分子动力学

GA-guided mD-VcMD: A genetic-algorithm-based method for multi-dimensional virtual-system coupled molecular dynamics

论文作者

Higo, Junichi, Kusaka, Ayumi, Kasahara, Kota, Kamiya, Narutoshi, Fukuda, Ikuo, Mori, Kentaro, Hata, Yutaka, Fukunishi, Yoshifumi

论文摘要

我们先前引入了一种构象采样方法,即通过计算机模拟增强生物分子系统的多维虚拟系统耦合分子动力学(MD-VCMD)。在这里,我们提出了一种新的采样方法,基于子区域的MD-VCMD,作为MD-VCMD的扩展。然后,我们使用遗传算法(GA)进一步扩展了基于子区域的方法,并将其命名为基于GA的MD-VCMD。由于生物分子系统的构象空间很大,因此单个模拟无法在整个构象空间中进行采样。然后,进行迭代模拟以逐渐增加采样区域。新方法具有以下优点:(1)这些方法免于生产运行:即,所有迭代中的所有快照都可以用于分析。 (2)这些方法没有重量函数的微调(概率分布函数或平均力的潜在)。 (3)一个简单的过程可以分配热力学重量来进行快照,尽管权重函数不用于进行迭代模拟。因此,由最终的快照产生了一个规范的合奏(即,一个热平衡的集合)。 (4)如果在抽样中出现了不良采样的区域,则可以将选择性抽样集中在不打破规范合奏的比例的情况下,以重点放置不良的区域。可以从规范合奏中获得生物分子系统的自由能景观。

We previously introduced a conformational sampling method, a multi-dimensional virtual-system coupled molecular dynamics (mD-VcMD), to enhance conformational sampling of a biomolecular system by computer simulations. Here, we present a new sampling method, subzone-based mD-VcMD, as an extension of mD-VcMD. Then, we further extend the subzone-based method using genetic algorithm (GA), and named it the GA-based mD-VcMD. Because the conformational space of the biomolecular system is vast, a single simulation cannot sample the conformational space throughout. Then, iterative simulations are performed to increase the sampled region gradually. The new methods have the following advantages: (1) The methods are free from a production run: I.e., all snapshots from all iterations can be used for analyses. (2) The methods are free from fine tuning of a weight function (probability distribution function or potential of mean force). (3) A simple procedure is available to assign a thermodynamic weight to snapshots sampled in spite that the weight function is not used to proceed the iterative simulations. Thus, a canonical ensemble (i.e., a thermally equilibrated ensemble) is generated from the resultant snapshots. (4) If a poorly-sampled region emerges in sampling, selective sampling can be performed focusing on the poorly-sampled region without breaking the proportion of the canonical ensemble. A free-energy landscape of the biomolecular system is obtainable from the canonical ensemble.

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