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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