Driven to near-experimental accuracy by refinement via molecular dynamics simulations
Driven to near-experimental accuracy by refinement via molecular dynamics simulations
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DOI：
10.1002/prot.25759
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发表时间：
2019-12-01
影响因子：
2.9
通讯作者：
Feig, Michael
中科院分区：
文献类型：
--
作者：
Heo, Lim;Arbour, Collin F.;Feig, Michael
蛋白质模型的优化是成功预测蛋白质结构的重要组成部分。基于分子动力学模拟的改进方法显示出蛋白质模型的一致性改进。自从对抽样构象进行总体平均的思想出现以来，在精化程度上已经取得了几年的进展。由于谐波约束，构象采样的多样性不足，CASP12的研究进展甚微。在CASP13期间，测试了一种新的细化方法，该方法比CASP12取得了显着改进。新方法旨在通过引入新特性来解决细化问题中的先前瓶颈。采用平底谐波约束代替谐波约束，迭代采样，采用新的评分函数和选择标准。新协议在减少计算成本的情况下扩展了构象采样。除了总体上的改进，一些模型得到了显著的改进，达到了接近实验的精度。
Protein model refinement has been an essential part of successful protein structure prediction. Molecular dynamics simulation-based refinement methods have shown consistent improvement of protein models. There had been progress in the extent of refinement for a few years since the idea of ensemble averaging of sampled conformations emerged. There was little progress in CASP12 because conformational sampling was not sufficiently diverse due to harmonic restraints. During CASP13, a new refinement method was tested that achieved significant improvements over CASP12. The new method intended to address previous bottlenecks in the refinement problem by introducing new features. Flat-bottom harmonic restraints replaced harmonic restraints, sampling was performed iteratively, and a new scoring function and selection criteria were used. The new protocol expanded conformational sampling at reduced computational costs. In addition to overall improvements, some models were refined significantly to near-experimental accuracy.