DOI: 10.3724/SP.J.1016.2013.02168

Chinese Journal of Computers (计算机学报) 2013/36:10 PP.2168-2178

Modeling the Structural Topology and Predicting the Three-Dimensional Structure for Transmembrane Helixes of GPCR

G protein-coupled receptors are a class of proteins characterized by α-helix bundle composed of seven transmembrane helixes. The prediction accuracy of bundle's three-dimensional structure directly affects the accuracy of the entire receptor, the accuracy of ligand complex, and structure-based functional analysis. After establishing a reasonable structural topology mapping the structural characters of transmembrane helixes, this paper develops a four-stage optimization method, introduces a new energy item for evaluating the bundle structure and constraints for tailoring sampling space to predict the three-dimensional structure of transmembrane helixes. Three in silio experiments are performed to evaluate the ability of the method. After comparing with structures submitted by GPCRDOCK2010 participants, the well-known structure prediction tools Swiss and MODELLER against eight resolved GPCR targets, respectively, the results show the method proposed in this paper obtains better accuracy on five targets than Swiss and gets lower TM RMSD on six targets and seven targets than single-and multi-template MODELLER respectively.

Key words:transmembrane helixes,G protein coupled receptor,structural topology,restraint

ReleaseDate:2014-07-21 17:04:05