Modelling of SARS-CoV-2 spike protein structures at varying pH values

Recognising the fact that the SARS-CoV-2 spike glycoprotein is the most crucial protein for the virus's attachment to surfaces and subsequent infection, we carried out massive all-atom molecular dynamics studies of the conformational states of S-protein in solvents of various pH values, ranging from pH = 1 through pH = 11. Our studies found that: (1) The S-protein’s structural deviation measured in the backbone at pH = 1 is 185% higher than that of pH = 7, and most of this overall deviation occurs at the receptor-binding domain and N-terminal domain. (2) Structural changes are also observed at both pH = 3 and pH = 11, albeit to a lesser extent than at pH = 1. (3) Changes, as measured by various metrics at pH = 5, pH = 7 and pH = 9, are insignificant. Such a high degree of structural tolerance of the S-protein at these pH values corroborates indirectly with in vitro observations that the virus retains significant infectivity over a wide range of pH. The multiscale structural analyses pinpoint the critical regions that are responsible for the S-protein’s structural deviations.