Microsecond simulation unravel the structural dynamics of SARS-CoV-2 Spike-C-terminal cytoplasmic tail (residues 1242-1273) (preprint)

ABSTRACT

Spike protein of human coronaviruses has been a vital drug and vaccine target. The multifunctionality of this protein including host receptor binding and apoptosis has been proved in several coronaviruses. It also interacts with other viral proteins such as membrane (M) protein through its C-terminal domain. The specific dibasic motif signal present in cytosolic region at C-terminal of spike protein helps it to localize within the endoplasmic reticulum (ER). However, the structural conformation of cytosolic region is not known in SARS-CoV-2 using which it interacts with other proteins and transporting vesicles. Therefore, we have demonstrated the 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 (residues 1242-1273). Also, in temperature dependent replica-exchange molecular dynamics simulations it has shown to form secondary structures. We believe that our findings will surely help us understand the structure-function relationship of the spike protein's cytosolic region.