Conformational preferences of triantennary and tetraantennary hybrid N-glycans in aqueous solution: Insights from 20 μs long atomistic molecular dynamic simulations.

In the current study, we have investigated the conformational dynamics of a triantennary ( N- glycan1) and tetraantennary ( N- glycan2) hybrid N- glycans found on the surface of the HIV glycoprotein using 20 μ s long all-atom molecular dynamics (MD) simulations. The main objective of the present study is to elucidate the influence of adding a complex branch on the overall glycan structural dynamics. Our investigation suggests that the average RMSD value increases when a complex branch is added to N- glycan1. However, the RMSD distribution is relatively wider in the case of N- glycan1 compared to N- glycan2, which indicates that multiple complex branches restrict the conformational variability of glycans. A similar observation is obtained from the principal component analysis of both glycans. All the puckering states ( 4 C 1 to 1 C 4 ) of each monosaccharide except mannose are sampled in our simulations, although the 4 C 1 chair form is energetically more favorable than 1 C 4 . In N- glycan1, the 1-6 linkage in the mannose branch [Man(9)- α (1-6)-Man(5)] stays in the gauche-gauche cluster, whereas it moves towards trans-gauche in N- glycan2. For both glycans, mannose branches are more flexible than the complex branches, and adding a complex branch does not influence the dynamics of the mannose branches. We have noticed that the end-to-end distance of the complex branch shortens by ∼ 10 Å in the presence of another complex branch. This suggests that in the presence of an additional complex branch, the other complex branch adopts a close folded structure. All these conformational changes involve the selective formation of inter-residue and water-mediated hydrogen-bond networks.