The Challenge to the Rule of Homology Modeling: Folding Mechanism Study of Protein GA and GB with High Sequence Identity but Different Native Structures

Author(s): Xue Wu , Zhong Jin , Zhilong Xiu , Guohui Li .

Journal Name: Current Pharmaceutical Design

Volume 19 , Issue 12 , 2013


As one of the most valuable methods for drug design, homology modeling shows that protein structures are more conserved than protein sequences, that is, the proteins with high sequence identity have high structural similarity, but protein pairs GA88/GB88 and GA95/GB95 prove the opposite. The pairs GA88 and GB88 shares the 88% sequence identity, but display different structures, and the pair GA95 and GB95 with 95% sequence identity yet presents different structures. The research on these proteins provides an opportunity of complementary study. In the process of protein folding, at which stage the protein final structure was determined and which residues were important for folding to a given structure were still unknown. Here we used OPLS all-atom force field for molecular dynamics simulations to study the unfolding of GA88, GB88, GA95 and GB95 at high temperatures, and used the process of protein unfolding to reverse the process of protein folding. GB88 and GB95 folded to the α+β structure, but GA88 and GA95 folded to the all-α-helix structure. In the process of GA88 and GA95 folding, the helices folded earlier than the formation of tertiary interactions. In the process of folding to GB88 and GB95, the α-helix formed earlier. We showed that early along the folding pathway, the final protein structure was confirmed, and very small differences between protein sequences determined the protein structure.

Keywords: Molecular dynamics simulation, Homology modeling, GA88, GB88, GA95, GB95, sequence identity, α-helix, protein sequences, protein structure.

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Article Details

Year: 2013
Page: [2282 - 2292]
Pages: 11
DOI: 10.2174/1381612811319120015
Price: $58

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