Interrelationship Between Protein Electrostatics and Evolution in HCV and HIV Replicative Proteins

TL;DR

This study explores how electrostatic properties of amino acids in HCV and HIV proteins relate to their evolutionary conservation, highlighting electrostatics' role in protein function and evolution.

Contribution

It reveals a correlation between electrostatic perturbations and conserved regions in HCV and HIV proteins, suggesting electrostatics influence protein evolution.

Findings

Highly conserved regions have more electrostatic perturbations.

Electrostatic states are linked to critical functional residues.

Electrostatics may guide protein evolution and function.

Abstract

Protein electrostatics have been demonstrated to play a vital role in protein functionality, with many functionally important amino acid residues exhibiting an electrostatic state that is altered from that of a normal amino acid residue. Residues with altered electrostatic states can be identified by the presence of a pKa value that is perturbed by 2 or more pK units, and such residues have been demonstrated to play critical roles in catalysis, ligand binding, and protein stability. Within the HCV helicase and polymerase, as well as the HIV reverse transcriptase, highly conserved regions were demonstrated to possess a greater number and magnitude of perturbations than lesser conserved regions, suggesting that there is an interrelationship present between protein electrostatics and evolution.