An assessment of the accuracy of the RRIGS hydration potential: Comparison to solutions of the Poisson–Boltzmann equation

Abstract

A rapid, pairwise hydration potential, the reduced radius independent Gaussian sphere (RRIGS) approximation, has been presented recently. Because experimental values of the conformational dependence of the hydration free energy are unavailable, this hydration potential is testable by comparison to a presumably more accurate (yet more computationally intensive) model. One such method is the electrostatic hydration approach, which models the protein as a collection of point charges in a low-dielectric medium and the solvent as a high-dielectric continuum. The electrostatic free energy can be determined by solving the Poisson–Boltzmann equation, which is carried out with the program DelPhi. The total free energy of hydration is calculated by adding a free energy of cavity formation term to this electrostatic term. Comparison is made for many conformations of two proteins, bovine pancreatic trypsin inhibitor (BPTI) and the carboxy-terminal fragment of the L7/L12 ribosomal protein (CTF). Thirty-nine near-native structures of BPTI, previously generated by Ripoll and coworkers, and 150 conformations of CTF, generated by a threading algorithm to cover a wide range of conformational space, were used in these comparisons. It is shown that, for the neutral forms of these proteins, the RRIGS hydration potential correlates very well with the electrostatic model hydration free energy, although the correlation is better for the CTF conformations than for the near-native BPTI conformations. For charged forms, the correlation is much poorer. These results serve as evidence that solvent-exposure models of hydration, which leave out cooperative effects between different groups, may be appropriate for modeling neutral or slightly charged species, because these cooperative effects are likely to be small. However, for highly charged species where cooperative effects are surely large, such an approach will be less accurate. © 1997 John Wiley & Sons, Inc. J Comput Chem 18:1072–1078, 1997