Figure 3.

Free energy cycles used to calculate exact (A) vs. two-body (B) side-chain/side-chain screened Coulombic energies (as shown in Equations 6 and 7, and 15 and 16, respectively). In each method, the electrostatic potential generated by side chain i is multiplied by the charges in side chain j to determine the screening energy between side chain i and side chain j. The key distinctions between the exact and two-body methods are as follows: The exact calculation uses the protein backbone and all of the side chains in the protein to define the dielectric boundary, while the two-body calculation uses the protein backbone and only two side chains to define the dielectric boundary. The parameters used in each FDPB calculation are indicated as follows: side chain i, shown in red, was assigned partial atomic charges from the PARSE charge set; the rest of the protein, when shown in gray, was assigned partial atomic charges of 0; side chain j, when shown in green, was assigned partial atomic charges of 0 in the FDPB calculation, but its PARSE partial atomic charges were used to obtain screening energies; the areas drawn in white were assigned a dielectric constant of 4 (protein interior); and the blue areas were assigned a dielectric constant of 80 (water) and a salt concentration of 50 mM.