Continuum Electrostatic Energies of Macromolecules in Aqueous Solutions

The efficient evaluation of electrostatic energies of macromolecules in aqueous solutions is useful for many problems in theoretical structural biology. A continuum method based on the generalized Born (GB) approximation is implemented here. It is shown that the choice of the dielectric discontinuity surface is critical for obtaining correct electrostatic energies of molecules in solution. In addition, it is demonstrated that an electrostatic model validated on solvation energies (vacuum to water transfer) might not be appropriate for energies in solution and might not yield correct energy ranking of ligand/protein complexes. The agreement between the GB approach and the finite difference solution of the Poisson equation is shown to be very good for both the molecular and the solvent accessible surface. The discrepancies between the GB and the finite difference approach are much lower than the ones due to the use of different surfaces.