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#compchem Just published in Chemical Science: Water-Glycan Interactions Drive the SARS-CoV-2 Spike Dynamics: Insights into Glycan-Gate Control and Camouflage Mechanism. Towards developing therapeutic strategies against #COVID19, we performed μs-long all-atom AMOEBA high-resolution polarizable adaptive sampling molecular dynamics simulations and zoomed in on the #SARSCoV2 interaction layers in open and... show more
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#compchem We uncovered: - that highly polarizable interfacial water, exclusively present in the open state, play a pivotal role in mediating interactions at glycan-gating patterns between N343 and N165 protein residues and their corresponding glycans. Additionally, the identification of distinct phases in open-state trajectories, namely Bridging, Clustering, Replacement, and Relaxation, elucidates water-mediated mechanisms at the protein-glycan interface. In contrast, the stability of the closed state may primarily result from internal protein and glycan interface reorganization rather than solvent-driven influences. Additionally, understanding solvent dynamics provides a deeper insight into the spike’s opening mechanism, presenting opportunities to prevent viral entry by targeting the water-mediated interactions at the glycan-gating sites that could potentially destabilize the open state and inhibit ACE2 binding. - Despite variations, our glycan-solvent accessibility analysis reveals the glycan shield capability to conserve constant interactions with the solvent, effectively camouflaging the virus from immune detection in both states. The presented insights advance our comprehension of viral pathogenesis at an atomic level, offering potential to combat COVID-19.

@ChemicalScience Congratulations
