Performance of protein-structure predictions with the physics-based UNRES force field in CASP11
Performance of protein-structure predictions with the physics-based UNRES force field in CASP11
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DOI：
10.1093/bioinformatics/btw404
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发表时间：
2016-11-01
期刊：
影响因子：
5.8
通讯作者：
Liwo, Adam
中科院分区：
文献类型：
--
作者：
Krupa, Pawel;Mozolewska, Magdalena A.;Liwo, Adam
作为Cornell-Gdansk小组的成员，我们使用基于物理学的粗粒度UNRES力场来预测第11届蛋白质结构预测技术关键评估社区实验（CASP 11）中的蛋白质结构。我们的方法涉及广泛的多重复制交换模拟的目标蛋白质与最近改进的UNRES力场，以提供更好的复制的局部结构的多肽链。所有的模拟都是从完全延伸的多肽链开始的，除了对二级结构的弱限制外，模拟过程中不包括外部信息，以使我们能够在允许的3周时间窗口内完成每个预测。由于简化了多肽链的UNRES表示，使用了增强的采样方法，代码优化和并行化以及足够的计算资源，我们首次能够处理所有55个人类预测目标，其大小从44到595个氨基酸残基，平均大小为251个残基。准确预测了6个单结构域蛋白的完整结构，其中T0769的准确度最高，其实验结构的97个残基的CaRMSD为3.8埃。正确的结构也预测了13个结构域的多结构域蛋白质的准确性相媲美的最好的基于模板的建模方法。随着目前正在进行的UNRES力场的进一步改进，我们基于物理学的粗粒度蛋白质结构预测方法最终将达到全局预测能力，因此，模拟蛋白质结构和动力学的可靠性在生化过程中非常重要。
Participating as the Cornell-Gdansk group, we have used our physics-based coarsegrained UNited RESidue (UNRES) force field to predict protein structure in the 11th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP11). Our methodology involved extensive multiplexed replica exchange simulations of the target proteins with a recently improved UNRES force field to provide better reproductions of the local structures of polypeptide chains. All simulations were started from fully extended polypeptide chains, and no external information was included in the simulation process except for weak restraints on secondary structure to enable us to finish each prediction within the allowed 3-week time window. Because of simplified UNRES representation of polypeptide chains, use of enhanced sampling methods, code optimization and parallelization and sufficient computational resources, we were able to treat, for the first time, all 55 human prediction targets with sizes from 44 to 595 amino acid residues, the average size being 251 residues. Complete structures of six singledomain proteins were predicted accurately, with the highest accuracy being attained for the T0769, for which the CaRMSD was 3.8 angstrom for 97 residues of the experimental structure. Correct structures were also predicted for 13 domains of multi-domain proteins with accuracy comparable to that of the best template-based modeling methods. With further improvements of the UNRES force field that are now underway, our physics-based coarse-grained approach to protein-structure prediction will eventually reach global prediction capacity and, consequently, reliability in simulating protein structure and dynamics that are important in biochemical processes.