3Drefine: Consistent protein structure refinement by optimizing hydrogen bonding network and atomic-level energy minimization

被引:134
作者
Bhattacharya, Debswapna
Cheng, Jianlin [1 ,2 ,3 ]
机构
[1] Univ Missouri, EBW 109, Dept Comp Sci, Columbia, MO 65211 USA
[2] Univ Missouri, Inst Informat, Columbia, MO 65211 USA
[3] Univ Missouri, Bond Life Sci Ctr, Columbia, MO 65211 USA
关键词
protein structure refinement; protein structure prediction; statistical potential; protein energy; hydrogen bonding network; energy minimization; STRUCTURE PREDICTION; MOLECULAR-DYNAMICS; MODELS; CONFORMATION; ACCURATE; CASP; RECOGNITION; SIMULATIONS; ALGORITHM; POSITIONS;
D O I
10.1002/prot.24167
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
One of the major limitations of computational protein structure prediction is the deviation of predicted models from their experimentally derived true, native structures. The limitations often hinder the possibility of applying computational protein structure prediction methods in biochemical assignment and drug design that are very sensitive to structural details. Refinement of these low-resolution predicted models to high-resolution structures close to the native state, however, has proven to be extremely challenging. Thus, protein structure refinement remains a largely unsolved problem. Critical assessment of techniques for protein structure prediction (CASP) specifically indicated that most predictors participating in the refinement category still did not consistently improve model quality. Here, we propose a two-step refinement protocol, called 3Drefine, to consistently bring the initial model closer to the native structure. The first step is based on optimization of hydrogen bonding (HB) network and the second step applies atomic-level energy minimization on the optimized model using a composite physics and knowledge-based force fields. The approach has been evaluated on the CASP benchmark data and it exhibits consistent improvement over the initial structure in both global and local structural quality measures. 3Drefine method is also computationally inexpensive, consuming only few minutes of CPU time to refine a protein of typical length (300 residues). 3Drefine web server is freely available at http://sysbio.rnet.missouri.edu/3Drefine/. Proteins 2013. (c) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:119 / 131
页数:13
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