For analysis of Electrostatic Potential and charge, hydrogen atoms are built into structures using the program REDUCE¹. Charges on amino acid atoms are set by applying the PARSE charge rules to amino acid structures². The PARSE charge model defines fractional charges for atoms including hydrogens, and is optimized for electrostatics. For simplicity we set pKa's of ionizable groups to that of model amino acids, and pH to 7.0. Disulfides are treated as neutral. Charges for nucleic acids are set from CNS parameter files³.

For electrostatic computations, we employ University of Houston Brownian Dynamics (UHBD)⁴, a widely used package that computes potentials by solving the finite difference Poisson-Boltzmann (FDPB) equation on a grid of points around the structure. For each protein, we compute two grids, a large one containing much solvent, and a medium-sized one close about the protein. Grid dimensions are determined automatically, dependent on the size of each protein; the medium sized grid has interpoint spacing between 0.6 and 2.6 Å.

Potentials are assigned to each surface atom by first choosing a point on the atom's exposed Van der Waals surface, near the center of the atom's exposed surface patch, where possible; then the potential at that point was evaluated by cubic interpolation from the nearest grid points. This avoids the problem of infinite potential at the centers of charges.

Typically, positive values of electrostatic potential occur near regions of positive charge, and negative potential values near regions of negative charge; but this may not be true in regions of strong electric field. Large changes in electrostatic potential, over short distances, correspond to strong electric field.

For Negative Electrostatic Potential, the computation is the same, except that the value assigned to each atom is multiplied by -1. Thus, typically, positive values occur near regions of negative charge, and negative values near regions of positive charge.

References:

1. Word, J.M., Lovell, S.C., Richardson, J.S. & Richardson, D.C. (1999). Asparagine and glutamine: using hydrogen atom contacts in the choice of amide side-chain orientation. J. Mol. Biol. 285, no. 4, 1735–1747.
2. Sitkoff, D., Sharp, K.A. & Honig, B. (1994). Accurate calculation of hydration free energies using macroscopic solvent models. J. Phys. Chem. 98, 1978.
3. Parkinson, G., Vojtechovsky, J., Clowney, L., Brunger, A.T., Berman, H.M. (1996). New parameters for the refinement of nucleic acid containing structures. Acta Cryst. D 52, 57-64.
4. Madura, J.D., Briggs, J.M., Wade, R.C., Davis, M.E., Luty, B.A., Ilin, A., Antosiewicz, J., Gilson, M.K., Bagheri, B., Scott, L.R, & McCammon, J.A. (1995). Comput. Phys. Commun. 91, 57.