  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.
