Evolutionary selectivity of amino acid is inspired from the enhanced structural stability and flexibility of the folded protein.

Aditya Rao, S J; Shetty, Nandini P

AIM The present study attempts to decipher the site-specific amino acid alterations at certain positions experiencing preferential selectivity and their effect on proteins' stability and flexibility. The study examines the selection preferences by considering pair-wise non-bonded interaction energies of adjacent and interacting amino acids present at the interacting site, along with their evolutionary history. MATERIALS AND METHODS For the study, variations in the interacting residues of spike protein (S-Protein) receptor-binding domain (RBD) of different coronaviruses were examined. The MD simulation trajectory analysis revealed that, though all the variants studied were structurally stable at their native and bound confirmations, the RBD of 2019-nCoV/SARS-CoV-2 was found to be more flexible and more dynamic. Furthermore, a noticeable change observed in the non-bonded interaction energies of the amino acids interacting with the receptor corroborated their selection at respective positions. KEY FINDINGS The conformational changes exerted by the altered amino acids could be the reason for a broader range of interacting receptors among the selected proteins. SIGNIFICANCE The results envisage a strong indication that the residue selection at certain positions is governed by a well-orchestrated feedback mechanism, which follows increased stability and flexibility in the folded structure compared to its evolutionary predecessor.