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 mu 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 (C-4(1) to C-1(4)) of each monosaccharide except mannose are sampled in our simulations, although the C-4(1) chair form is energetically more favorable than C-1(4). In N-glycan1, the 1-6 linkage in the mannose branch [Man(9)-alpha(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 similar to 10 angstrom 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.

Automated summary

In this study, the conformational dynamics of complex glycans on the surface of HIV glycoprotein were investigated using molecular dynamics simulations. The results reveal the influence of adding complex branches on the overall glycan structural dynamics and provide insights into the flexibility and conformational changes of different glycan branches.