AWSEM-MD: Protein Structure Prediction Using Coarse-Grained Physical Potentials and Bioinformatically Based Local Structure Biasing

被引:238
作者
Davtyan, Aram [2 ,3 ]
Schafer, Nicholas P. [1 ]
Zheng, Weihua [4 ]
Clementi, Cecilia [1 ]
Wolynes, Peter G. [1 ,4 ]
Papoian, Garegin A. [2 ,3 ]
机构
[1] Rice Univ, Dept Chem, Houston, TX 77251 USA
[2] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA
[3] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA
[4] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA
基金
美国国家科学基金会;
关键词
TERTIARY STRUCTURE RECOGNITION; ASSOCIATIVE MEMORY HAMILTONIANS; MOLECULAR-DYNAMICS; ENERGY LANDSCAPE; HOMOLOGY; MODELS; WATER;
D O I
10.1021/jp212541y
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
The associative memory, water mediated, structure and energy model (AWSEM) is a coarse-grained protein force field. AWSEM contains physically motivated terms, such as hydrogen bonding, as Well as a bioinformatically based local structure biasing term, which efficiently takes into account many-body effects that are modulated by the local sequence. When combined with appropriate local or global alignments to choose memories, AWSEM can be used to perform de novo protein structure prediction. Herein we present structure prediction results for a particular choice of local sequence alignment method based on short residue sequences called fragments. We demonstrate the model's structure prediction capabilities for three levels of global homology between the target sequence and those proteins used for local structure biasing, all of which assume that the structure of the target sequence is not known. When there are no homologues in the database of structures used for local structure biasing, AWSEM calculations produce structural predictions that are somewhat improved compared with prior works using related approaches. The inclusion of a small. number of structures from homologous sequences improves structure prediction only marginally, but when the fragment search is restricted to only homologous sequences, AWSEM can perform high resolution structure prediction and can. be used for kinetics and dynamics studies.
引用
收藏
页码:8494 / 8503
页数:10
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