SARS-CoV-2 spike binding to ACE2 is stronger and longer ranged due to glycan interaction

Abstract

Highly detailed steered Molecular Dynamics simulations are performed on differently glycosylated receptor binding domains of the SARS-CoV-2 spike protein. The binding strength and the binding range increases with glycosylation. The interaction energy rises very quickly with pulling the proteins apart and only slowly drops at larger distances. We see a catch slip type behavior where interactions during pulling break and are taken over by new interactions forming. The dominant interaction mode are hydrogen bonds but Lennard-Jones and electrostatic interactions are relevant as well.

When the Dust Has Settled: Calculation of Binding Affinities from First Principles for SARS-CoV-2 Variants with Quantitative Accuracy

“…Following the same steps as in the other calculations, we found a slightly smaller (about −1 kcal/mol) binding free energy at −10.8 kcal/mol, compared to that of the minimally glycosylated model (−11.5 kcal/mol). This is in subtle contrast to recent experiments, in which the presence of glycans was found to contribute about +1 kcal/mol to the binding (−10.3 kcal/mol for the fully glycosylated complex and −9.7 kcal/mol for that devoid of glycans) . Regardless, our calculated binding free energy for the fully glycosylated complex falls within the range observed experimentally, which spans 4 k B T (−9.0, −10.3, and −11.4 kcal/mol).…”

Significance of the RBD mutations in the SARS-CoV-2 omicron: from spike opening to antibody escape and cell attachment

“…A475–S19) in omicron compared to WT. Since the presence of glycans at the interface can enhance the RBD–ACE2 interactions, 42 we calculated the hydrogen bonding with glycan at N90 at the interface and found that omicron has a relatively stronger interaction with 80% hydrogen bond occupancy in omicron vs. 56% in delta.…”

A computational algorithm to assess the physiochemical determinants of T cell receptor dissociation kinetics

“…This characterization provides an overall assessment of the physiochemical features that might impact bond lifetime and is consistent with the quaternary structure of globular proteins. We considered features likely to impact dissociation kinetics and thus included H-bonds (58) , LJ- contacts (59) , distance between the TCR and pMHC [60] , [61] , solvent accessible surface area (SASA) (62) , root mean square fluctuations (RMSF) (63) , and the gyration tensor of the TCR and pMHC. This approach resulted in 18 features for the first set, and we dubbed these quaternary features ( Table S2 ).…”