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

Abstract

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 μs 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 (⁴C₁ to ¹C₄) of each monosaccharide except mannose are sampled in our simulations, although the ⁴C₁ chair form is energetically more favorable than ¹C₄. 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.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

Keywords:

• Hybrid N-glycans
• molecular dynamics
• PCA
• phi/psi
• puckering angle

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics

There is no human or animal experiment in this study.

Data availability statement

The data that support the findings of this study are available from the corresponding author (PK) upon reasonable request.

Additional information

Funding

This work was supported by the Department of Biotechnology, Govt. of India (grant number BT/RLF/Re-entry/40/2014), and the Department of Science and Technology, Govt. of India (grant number ECR/2017/000010 and DST/NSM/R&D_HPC_Applications/2021/03.18).