Molecular dynamics simulations on the conformational transitions from the GA 98 (GA 88) to GB 98 (GB 88) proteins

Abstract

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 3α G_A 98 (G_A 88) state to the α+4β 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 αA and αC, then the traversing of αB, and the formation of the 4β 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 αB 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 © 2016 John Wiley & Sons, Ltd.

Keywords: GA98 (GA88); GB98 (GB88); molecular dynamics simulations; protein G of group C and G Streptococci; transition mechanism.