All-Atom Steered Molecular Dynamics Simulations of Large Proteins in a Small Water Box
All-Atom Steered Molecular Dynamics Simulations of Large Proteins in a Small Water Box
复制标题
小水箱中大蛋白质的全原子引导分子动力学模拟
DOI：
10.1016/j.bpj.2018.11.1770
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发表时间：
2019
影响因子：
3.4
通讯作者：
Marszalek, Piotr E.
中科院分区：
文献类型：
--
作者：
Wang, David;Marszalek, Piotr E.
转向分子动力学（SMD）模拟补充力谱实验表明，结构变化与力延伸数据。通常，大蛋白质的操纵分子动力学模拟是通过粗粒度（CG）模型进行的，这是由于模拟大蛋白质的SMD拉伸的计算费用。特别是，使用全原子系统需要创建一个非常大的水箱，以容纳一个完全延伸的多肽链。例如，为了对10500个残基长的蛋白质进行全原子SMD模拟，需要200 nm长的水箱以允许多肽骨架的完全延伸。系统总尺寸超过160万个原子，因此在相当慢的拉伸速度下，SMD轨迹计算在大多数计算机系统上都是不切实际的冗长。在这里，通过执行分段SMD拉伸的大蛋白质在一个10倍减少水箱，我们试图分析是否在这种条件下进行的拉伸模拟可以复制力谱扩展数据，以及这些结果是否同意利用减少表示的生物分子的模拟。对于我们的系统，我们发现，SMD模拟减少水箱可以在合理的时间内完成，并通过全原子SMD给出的结果不同于通过粗粒度模拟。这些结果表明，全原子SMD可以提供额外的细节层，这可能有助于解释力延伸数据和设计新的实验。
Steered molecular dynamics (SMD) simulations complement force spectroscopy experiments by suggesting which structural changes are associated with force extension data. Typically, steered molecular dynamics simulations of large proteins are done via coarse-grained (CG) models due to the computational expense of simulated SMD stretching of large proteins. In particular, using all-atom systems requires the creation of a very large water box to accommodate a completely extended polypeptide chain. For example, to carry out all-atom SMD simulations of∼ 500 residue long proteins, one needs a 200 nm-long water box to allow complete extension of the polypeptide backbone. The total system size then exceeds 1.6 million atoms thereby making SMD trajectory calculations, at reasonably slow stretching velocities, impractically lengthy on most computer systems. Here, by performing piece-wise SMD stretching of a large protein in a 10-fold reduced water box, we attempt to analyze whether a stretching simulation conducted under such conditions can replicate force spectroscopy extension data and whether these results agree with simulations utilizing reduced representations of biomolecules. For our system, we find that a SMD simulation in the reduced water box can be completed in a reasonable amount of time and the results given by all-atom SMD differ from those given through a coarse-grained simulation. These results suggest that all-atom SMD can provide an extra layer of detail which may be helpful in interpreting force extension data and designing new experiments.