title: GEM: a Gaussian Evolutionary Method for predicting protein side-chain conformations.
abstract: We have developed an evolutionary approach to predicting protein side-chain conformations. This approach, referred to as the Gaussian Evolutionary Method (GEM), combines both discrete and continuous global search mechanisms. The former helps speed up convergence by reducing the size of rotamer space, whereas the latter, integrating decreasing-based Gaussian mutations and self-adaptive Gaussian mutations, continuously adapts dihedrals to optimal conformations. We tested our approach on 38 proteins ranging in size from 46 to 325 residues and showed that the results were comparable to those using other methods. The average accuracies of our predictions were 80% for chi(1), 66% for chi(1 + 2), and 1.36 A for the root mean square deviation of side-chain positions. We found that if our scoring function was perfect, the prediction accuracy was also essentially perfect. However, perfect prediction could not be achieved if only a discrete search mechanism was applied. These results suggest that GEM is robust and can be used to examine the factors limiting the accuracy of protein side-chain prediction methods. Furthermore, it can be used to systematically evaluate and thus improve scoring functions.
authors.affiliation: Department of Biological Science and Technology and Institute of Bioinformatics, National Chiao Tung University, Hsinchu, 30050, Taiwan. moon@cc.nctu.edu.tw
authors.forename: Jinn-Moon
authors.initials: JM
authors.lastname: Yang
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Tsai
authors.forename: Ming-Jing
authors.initials: MJ
authors.lastname: Hwang
authors.forename: Huai-Kuang
authors.initials: HK
authors.lastname: Tsai
authors.forename: Jenn-Kang
authors.initials: JK
authors.lastname: Hwang
authors.forename: Cheng-Yan
authors.initials: CY
authors.lastname: Kao
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry / Q000145:classification; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D008956:Models, Chemical; D016296:Mutagenesis; D019151:Peptide Library; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D011995:Recombination, Genetic; D055672:Static Electricity; D013223:Statistics as Topic; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D019151:Peptide Library; D011506:Proteins