Effect of N343 glycosylation and N501Y mutation on the SARS-CoV-2 spike protein: Modeling and MD Simulations

The effect of N343 glycosylation and N501Y mutation on the SARS-CoV-2 spike protein was investigated using molecular dynamics (MD) simulations of the complex of the receptor binding domain (RBD) of the spike protein and angiotensin converting enzyme 2 (ACE2). Before conducting MD simulations, we modified the atomic charge model of histidine bound to a zinc ion. MD simulations showed that the interaction energy between the RBD and ACE2 was significantly affected by both N343 glycosylation and N501Y mutation. Although N501Y mutation decreased the interaction energy, we found that N501Y mutation significantly enhanced the fluctuation of several parts of the protein complex, which may result in an entropic contribution. This might be a clue to understand why N501Y mutation increases the binding affinity of the spike protein and ACE2.