Atomic-level protein structure refinement using fragment-guided molecular dynamics conformation sampling.
Atomic-level protein structure refinement using fragment-guided molecular dynamics conformation sampling.
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DOI：
10.1016/j.str.2011.09.022
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发表时间：
2011-12-07
期刊：
影响因子：
5.7
通讯作者：
Zhang, Yang
中科院分区：
文献类型：
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作者：
Zhang, Jian;Liang, Yu;Zhang, Yang
分子动力学（MD）模拟在蛋白质结构精化中的关键困难之一是基于物理的能量景观缺乏中程漏斗来引导非天然构象接近天然状态。我们建议使用的目标模型作为探针，以确定从PDB片段类似物。然后使用距离图来重新塑造MD能量漏斗。该协议在181个基准和26个CASP目标上进行了测试。发现具有TM分数>0.5的正确折叠的结构模型通常可以被拉得更接近具有更高GDT-HA分数的天然结构模型;但是对于不正确折叠（TM分数<0.5）的模型的改善不太明显。这些数据表明，基于模板的碎片距离图基本上重新塑造了MD能量景观从高尔夫球场般的漏斗状的成功细化的目标与TM得分~0.5的半径。这些结果展示了一种新的途径，以提高高分辨率的结构相结合的知识为基础的模板信息与基于物理的MD模拟。
One of critical difficulties of molecular dynamics (MD) simulations in protein structure refinement is that the physics-based energy landscape lacks of middle-range funnel to guide non-native conformations towards near-native states. We propose to use the target model as probe to identify fragmental analogs from PDB. The distance maps are then used to re-shape the MD energy funnel. The protocol was tested on 181 benchmarking and 26 CASP targets. It was found that structure models of correct folds with TM-score>0.5 can be often pulled closer to native with higher GDT-HA score; but improvement for the models of incorrect folds (TM-score<0.5) are much less pronounced. These data indicate that template-based fragmental distance maps essentially re-shaped the MD energy landscape from golf-course-like to funnel-like ones in the successfully-refined targets with a radius of TM-score~0.5. These results demonstrate a new avenue to improve high-resolution structures by combining knowledge-based template information with physics-based MD simulations.
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