Simulation Time Required for Diminishing the Initial Conformational Deviations among Protein Crystal Structures
Simulation Time Required for Diminishing the Initial Conformational Deviations among Protein Crystal Structures
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DOI：
10.1021/acs.jpcb.8b04800
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发表时间：
2018-09-13
影响因子：
3.3
通讯作者：
Hoshino, Tyuji
中科院分区：
文献类型：
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作者：
Qi, Fei;Yoneda, Tomoki;Hoshino, Tyuji
单一种类蛋白质的多种晶体结构通常可以根据它们的构象偏差分为几组。导致结构分离的主要因素是晶体的空间群，其中沉淀剂对晶体中蛋白质的堆积具有强烈的影响。在这项研究中，我们研究了分离的蛋白质晶体结构组是否可以合并成一个组，通过计算机模拟没有沉淀剂。以鸡卵清溶菌酶（HEWL）、肌红蛋白（Mb）、血红蛋白（Hb）和人血清白蛋白（HSA）的晶体结构为研究对象，进行分子动力学（MD）模拟。例如，对HEWL进行了25次MD模拟，其中从不同的晶体结构构建了25个计算模型。聚类分析应用于在相同的时间点从各自的模拟轨迹获得的25个快照结构，并且在模拟期间每5 ns重复聚类分析。因此，除了少数例外，分离的集群组基本上合并为一个组。在HEWL中，加热后观察到晶体结构的明显构象变化。模拟结构对初始晶体的依赖性减弱，在20 ns的MD模拟下，所有的团簇都合并成一组。在Mb中，所有簇在10 ns时合并为一组。对于Hb和HSA，合并结构所需的时间变得更长。在血红蛋白，初始组分离后逐渐变得模糊不清的预平衡，和所需的时间为减少对晶体结构的依赖性是130纳秒，除了一个集群组。在HSA中，160 ns是必要的所有集群合并成一个组。这些时间为判断蛋白质模拟的平衡性提供了重要指标。
Multiple crystal structures of a single kind of protein can be generally separated into several groups from their conformational deviations. A major factor causing the structural separation is the space group of crystals, in which precipitating agents have a strong influence on the packing of proteins in a crystal. In this study, we examined whether the separated groups of protein crystal structures can be merged into one group by computer simulation without a precipitating agent. The crystal structures of hen egg-white lysozyme (HEWL), myoglobin (Mb), hemoglobin (Hb), and human serum albumin (HSA) were selected as samples for molecular dynamics (MD) simulation. For example, 25 MD simulations were performed for HEWL, with 25 computational models being built from different crystal structures. Cluster analysis was applied to 25 snapshot structures obtained at the same time point from the respective simulation trajectories and the cluster analysis was repeated every 5 ns during the simulations. As a result, the separated cluster groups were basically merged into one group with only a few exceptions. In HEWL, noticeable conformational changes from the crystal structures were observed after heating. The dependence of the simulated structures on the initial crystals was diminished, and all of the clusters were merged into one group at 20 ns of MD simulation. In Mb, all of the clusters were merged into one group at 10 ns. For Hb and HSA, the time necessary for merging the structures became longer. In Hb, the initial group separation gradually became ambiguous after pre-equilibration, and the time required for diminishing the dependence on the crystal structure was 130 ns except for one cluster group. In HSA, 160 ns was necessary for all of the clusters to be merged into one group. These times provide important index for judging the equilibration of protein simulations.