Time Dependent Dihedral Angle Oscillations of the Spike Protein of SARS-CoV-2 Reveal Favored Frequencies of Dihedral Angle Rotations

Abstract

The spike protein of SARS-CoV-2 is critical to viral infection of host cells which ultimately results in COVID-19. In this study we analyze the behavior of dihedral (phi and psi) angles of the spike protein over time from molecular dynamics and identify that the oscillations of these dihedral angles are dominated by a few discrete, relatively low frequencies in the 23-63 MHz range with 42.96875 MHz being the most prevalent frequency sampled by the oscillations. We further observe that upon tallying the populations of each individual frequency for all residues along the frequency spectrum, there is a regular alternation between high and low population counts along the increasing frequency values in the spectrum. This alternation of the counts becomes less pronounced and ultimately stabilizes as the frequency values increase. These observations thus suggest a regularity and propensity in the spike proteins dihedral angles to avoid similar oscillation population counts between vicinal frequencies. We also observe that for amino acids that are least abundant in the S protein, there are certain frequencies at which the dihedral angles never oscillate, in contrast to relatively abundant amino acids that ultimately cover the entire spectrum. This suggests that the frequency components of dihedral angle oscillations may also be a function of position in the primary structure: the more positions an amino acid is found in, the more frequencies it can sample. Lastly, certain residues identified in the literature as constituting the inside of a druggable pocket of the spike protein, as well as other residues identified as allosteric sites, are observed in our data to have distinctive time domain profiles. This motivates us to propose residues from our dynamic data, with similar time domain profiles, which may be of potential interest to the vaccine and drug design communities, for further investigation. Thus our findings indicate that there is a particular frequency domain profile for the spike protein, hidden within the time domain data, and this information, perhaps with the suggested residues, might provide additional insight into therapeutic development strategies for COVID-19 and beyond.