Impact of a Poisson-Boltzmann electrostatic restraint on protein structures refined at medium resolution

The Poisson-Boltzmann formulism has been developed as a restraint for electrostatic interactions during the crystallographic refinement of macromolecules. It accounts implicitly for the effects of solvent and mobile ions, which are usually not included as restraints in the refinement of experimental structures. The electrostatic restraint has been implemented by combining software for numerically solving the three-dimensional Poisson-Boltzmann equation with a package for stereochemically restrained refinement. Its application to medium-resolution protein structures leads to a reduced free R factor, overfitting and to improved interactions in salt bridges and between polar or charged amino acids and the solvent. In contrast, Coulombic and screened Coulombic treatments did not lead to significant gains. The work leads to a modest improvement in refinement methods, confirmation that the Poisson-Boltzmann formulism is more consistent with experimental structure than the Coulombic approach, and to a reduction in the discrepancy between experimental and electrostatically optimized atomic models.