Microsecond simulations and CD spectroscopy reveals the intrinsically disordered nature of SARS-CoV-2 spike-C-terminal cytoplasmic tail (residues 1242-1273) in isolation.

ABSTRACT

All available SARS-CoV-2 spike protein crystal and cryo-EM structures have shown missing electron densities for cytosolic C-terminal regions (CTR). Generally, the missing electron densities point towards the intrinsically disordered nature of the protein region (IDPR). This curiosity has led us to investigate the cytosolic CTR of the spike glycoprotein of SARS-CoV-2 in isolation. The spike CTR is supposed to be from 1235 to 1273 residues or 1242-1273 residues based on our used prediction. Therefore, we have demonstrated the structural conformation of cytosolic region and its dynamics through computer simulations up to microsecond timescale using OPLS and CHARMM forcefields. The simulations have revealed the unstructured conformation of cytosolic region. Further, we have validated our computational observations with circular dichroism (CD) spectroscopy-based experiments and found its signature spectra at 198 nm. We believe that our findings will surely help in understanding the structure-function relationship of the spike protein's cytosolic region.