Simulation of Protein Folding Process

蛋白质折叠过程模拟

基本信息

批准号：
15300101
负责人：
GO Mitiko
金额：
$ 10.62万
依托单位：
Ochanomizu University (2005)Nagahama Institute of Bio-Science and Technology (2003-2004)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15300101/
关键词：
Protein folding Module Molecular dynamics simulation Protein G Barnase Hierarchical formation Hydrophobic core Secondary structure AMBER protein G 力場パラメタ

项目摘要

Despite huge degree of conformational freedom, protein can fold into its specific native structure within a physiological time scale. To elucidate its mechanism, we performed heat-induced unfolding simulations of barnase and protein G.For barnase, performing ten runs of molecular dynamics simulations at 498 K, we characterized a common feature on unfolding processes. Hydrophobic cores and secondary structures seen in the native state were gradually disrupted until they were all eventually lost except some very local regions kept their native-like conformations. This is consistent with known experimental results. Our novel finding is that the native hierarchical structure composed of compact substructures, called modules, were well sustained in such extensive unfolded states in a sense that segmental regions corresponding to the native modules kept relatively compact conformations despite the whole protein structure largely inflated. Furthermore, hydrophobic interactions between both te … More rmini of modules were retained with high probability, which would be a main factor to stabilize module structures.For protein G, although early simulation results were inconsistent with known experiments, reconsidering simulation conditions revealed that the problem was likely ascribed to lower dielectric constants at higher simulation temperatures. And then, by using a less stable mutant or reduced-charge conditions, we obtained simulation results consistent with the experiments. Analyzing these simulation data, we found a similar unfolding feature to that of barnase, that is, native-like hierarchical structures composed of relatively compact substructures had a tendency to be sustained despite large disruption of hydrophobic cores and secondary structures occurred as unfolding proceeded.In conclusion, formation of module structures in an early stage of folding process could be a key to solve the folding problem, that is, a key to reduce conformational space to be searched for the native structure. Less

尽管构象自由度很大，但蛋白质仍可以在物理时间尺度内折叠成其特定的本地结构。为了阐明其机制，我们进行了热诱导的barnase和蛋白质G. for barnase的展开模拟，在498 K处进行了十次分子动力学模拟，我们表征了在展开过程中的共同特征。在本地状态下看到的疏水核心和二级结构逐渐破坏，直到最终都丢失，除非一些非常本地的地区保持其本地样构象。这与已知的实验结果一致。我们的新发现是，在如此广泛的展开状态下，由紧凑型子结构组成的天然层次结构在某种意义上在分段区域对应于天然模块相对应保持相对紧凑的构象中，尽管整个蛋白质结构在很大程度上膨胀了。 Furthermore, Hydrophobic interactions between both te … More rmini of modules were retained with high probability, which would be a main factor to stabilize module structures.For protein G, although early simulation results were inconsistent with known experiments, reconsidering simulation conditions revealed that the problem was likely assigned to lower dieelectric constants at higher simulation temperatures.然后，通过使用较不稳定的突变体或降低的电荷条件，我们获得了与实验一致的仿真结果。分析这些模拟数据时，我们发现了与巴尔米酶相似的展开特征，即由天然的层次结构组成的类似的层次结构，相对紧凑的子结构组成的趋势是持续的目的地，对疏水核心的持续大量破坏和次级结构发生了，随着不展开的不断发展，在早期阶段的结构中，构成了一个折叠的构成，这是折叠的结构。要搜索天然结构的空间。较少的