Molecular dynamics simulations on the conformational transitions from the GA98 (GA88) to GB98 (GB88) proteins

We performed conventional and targeted molecular dynamics simulations to address the dynamic transition mechanisms of the conformational transitions from the G(A)98 protein with only 1 mutation of Leu45Tyr to G(B)98 and from the G(A)88 protein with 7 mutations of Gly24Ala, Ile25Thr, Ile30Phe, Ile33Tyr, Leu45Tyr, Ile49Thr, and Leu50Lys to G(B)88. The results show that the conformational transition mechanism from the mutated 3 G(A)98 (G(A)88) state to the +4 G(B)98 (G(B)88) state via several intermediate conformations involves the bending of loops at the N and C termini firstly, the unfolding of A and C, then the traversing of B, and the formation of the 4 layer with the conversion of the hydrophobic core. The bending of loops at the N and C termini and the formation of the crucial transition conformation with the full unfolded structure are key factors in their transition processes. The communication of the interaction network, the bending directions of loops, and the traversing site of B in the transition of G(A)98 to G(B)98 are markedly different from those in G(A)88 to G(B)88 because of the different mutated residues. The analysis of the correlations and the calculated mass center distances between some segments further supported their conformational transition mechanisms. These results could help people to better understand the Paracelsus challenge. Copyright (c) 2016 John Wiley & Sons, Ltd.