Consistent refinement of submitted models at CASP using a knowledge-based potential

被引:38
作者
Chopra, Gaurav [1 ]
Kalisman, Nir [1 ]
Levitt, Michael [1 ]
机构
[1] Stanford Univ, Stanford Sch Med, Dept Biol Struct, Stanford, CA 94305 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
refinement; comparative modeling; CASP7; ENCAD; MESHI; knowledge-based; stereochemistry; PROTEIN-STRUCTURE PREDICTION; ENERGY MINIMIZATION; MOLECULAR-DYNAMICS; LOW-RESOLUTION; NUCLEIC-ACIDS; CONFORMATIONS; OPTIMIZATION; ACCURATE; ROSETTA; DENSITY;
D O I
10.1002/prot.22781
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein structure refinement is an important but unsolved problem; it must be solved if we are to predict biological function that is very sensitive to structural details. Specifically, critical assessment of techniques for protein structure prediction (CASP) shows that the accuracy of predictions in the comparative modeling category is often worse than that of the template on which the homology model is based. Here we describe a refinement protocol that is able to consistently refine submitted predictions for all categories at CASP7. The protocol uses direct energy minimization of the knowledge-based potential of mean force that is based on the interaction statistics of 167 atom types (Summa and Levitt, Proc Natl Acad Sci USA 2007; 104:3177-3182). Our protocol is thus computationally very efficient; it only takes a few minutes of CPU time to run typical protein models (300 residues). We observe an average structural improvement of 1% in GDT_TS, for predictions that have low and medium homology to known PDB structures (Global Distance Test score or GDT_TS between 50 and 80%). We also observe a marked improvement in the stereochemistry of the models. The level of improvement varies amongst the various participants at CASP, but we see large improvements (>10% increase in GDT_TS) even for models predicted by the best performing groups at CASP7. In addition, our protocol consistently improved the best predicted models in the refinement category at CASP7 and CASP8. These improvements in structure and stereochemistry prove the usefulness of our computationally inexpensive, powerful and automatic refinement protocol. Proteins 2010; 78:2668-2678. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:2668 / 2678
页数:11
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