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

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) receptorbinding
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.