期刊
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
卷 79, 期 9, 页码 2693-2710出版社
WILEY-BLACKWELL
DOI: 10.1002/prot.23099
关键词
protein pK(a); amino acid pK(a); pK(a) modeling; protein ionization properties; TSAR
资金
- European Community [FP7/2007-2013, 227279]
- Foundation for Assistance to Small Enterprises in the Scientific Area [6332p/7168]
A new graph-theoretical approach called thermodynamic sampling of amino acid residues (TSAR) has been elaborated to explicitly account for the protein side chain flexibility in modeling conformation-dependent protein properties. In TSAR, a protein is viewed as a graph whose nodes correspond to structurally independent groups and whose edges connect the interacting groups. Each node has its set of states describing conformation and ionization of the group, and each edge is assigned an array of pairwise interaction potentials between the adjacent groups. By treating the obtained graph as a belief-network-a well-established mathematical abstraction-the partition function of each node is found. In the current work we used TSAR to calculate partition functions of the ionized forms of protein residues. A simplified version of a semi-empirical molecular mechanical scoring function, borrowed from our Lead Finder docking software, was used for energy calculations. The accuracy of the resulting model was validated on a set of 486 experimentally determined pK(a) values of protein residues. The average correlation coefficient (R) between calculated and experimental pK(a) values was 0.80, ranging from 0.95 (for Tyr) to 0.61 (for Lys). It appeared that the hydrogen bond interactions and the exhaustiveness of side chain sampling made the most significant contribution to the accuracy of pK(a) calculations.
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