“…Much of this work includes identification of functionally-relevant residues in biomolecules by looking at electrostatic destabilization of conserved residues [18], highly shifted pK a values [44], clusters of charged residues [59], protein-membrane interactions [40], and other structural characteristics [55]. Other research has focused on comparisons of electrostatic potentials including global analyses of the biomolecular structure [38,9,40,51,37,30,36,47,43,8,53,34,46,35,52] both in threedimensional space over the entire biomolecular structure and at localized regions such as active sites [52,6,22]. While the past characterization of electrostatic properties of biomolecules has provided insight into a variety of biomolecular properties, previous applications focused only on a few quantitative measures of electrostatic properties and, with a few exceptions [8,57], limited their studies to relatively small numbers of biomolecules.…”