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 human host cells which ultimately results in COVID-19. In this study we analyzed the behavior of dihedral angles (phi and psi) of the wild-type spike protein over time from molecular dynamics and identified that their oscillations are dominated by a few discrete, relatively low frequencies in the 23–63 MHz range with 42.969 MHz being the most prevalent frequency sampled by the oscillations. We thus observed the spike protein to favor certain frequencies more than others. Gaps in the tally of all observed frequencies for low-abundance amino acids also suggests that the frequency components of dihedral angle oscillations may be a function of position in the primary structure since relatively more abundant amino acids lacked gaps. Lastly, certain residues identified in the literature as constituting the inside of a druggable pocket, as well as others identified as allosteric sites, are observed in our data to have distinctive time domain profiles. This motivated us to propose additional residues with similar time domain profiles, which may be of potential interest to the vaccine and drug design communities for further investigation. Thus these 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.