Interrelationship Between Protein Electrostatics and Evolution in HCV   and HIV Replicative Proteins
  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. 
Christopher M. Frenz