GEM: a Gaussian Evolutionary Method for predicting protein side-chain conformations.
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.
Yang
Jinn-Moon
JM
Department of Biological Science and Technology and Institute of Bioinformatics, National Chiao Tung University, Hsinchu, 30050, Taiwan. moon@cc.nctu.edu.tw
Tsai
Chi-Hung
CH
Hwang
Ming-Jing
MJ
Tsai
Huai-Kuang
HK
Hwang
Jenn-Kang
JK
Kao
Cheng-Yan
CY
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
D000596:Amino Acids; D019151:Peptide Library; D011506:Proteins