Release Time:2019-03-09  Hits:

Indexed by: Journal Article

Date of Publication: 2013-04-01

Journal: CURRENT PHARMACEUTICAL DESIGN

Included Journals: Scopus、SCIE

Volume: 19

Issue: 12

Page Number: 2282-2292

ISSN: 1381-6128

Key Words: Molecular dynamics simulation; Homology modeling; G(A)88; G(B)88; G(A)95; G(B)95

Abstract: 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 G(A)88/G(B)88 and G(A)95/G(B)95 prove the opposite. The pairs G(A)88 and G(B)88 shares the 88% sequence identity, but display different structures, and the pair G(A)95 and G(B)95 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 G(A)88, G(B)88, G(A)95 and G(B)95 at high temperatures, and used the process of protein unfolding to reverse the process of protein folding. G(B)88 and G(B)95 folded to the alpha+beta structure, but G(A)88 and G(A)95 folded to the all-alpha-helix structure. In the process of G(A)88 and G(A)95 folding, the helices folded earlier than the formation of tertiary interactions. In the process of folding to G(B)88 and G(B)95, the alpha-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.