Optimized Radii for Poisson−Boltzmann Calculations with the AMBER Force Field

Abstract

Implicit solvent models are a standard tool for assessing the electrostatics of biomolecular systems. The accuracy of quantitative predictions, such as pKa values, transfer free energies, binding energies, and solvation forces, is strongly dependent on one's choice of continuum parameters: the solute charges, dielectric coefficient, and radii, which define the dielectric boundary. To ensure quantitative accuracy, these parameters can be benchmarked against explicit solvent simulations. Here we present two sets of optimized radii to define either abrupt or cubic-spline smoothed dielectric boundaries in Poisson-Boltzmann calculations of protein systems with AMBER (parm99) charges. Spline smoothing stabilizes the electrostatic potential at the molecular surface, allowing for continuum force calculations. Most implementations, however, require significantly different radii than the abrupt boundary surfaces. The optimal continuum radii are initially approximated from the solvent radial charge distribution surrounding each atom type. A genetic algorithm is then used to fine-tune the starting values to reproduce charging free energies measured from explicit solvent simulations. The optimized radii are tested on four protein-like polypeptides. The results show increased accuracy of molecular solvation energies and atomic forces relative to commonly used continuum parameter sets. These radii are suitable for Poisson-Boltzmann calculations with the AMBER force field and offer energetic congruence to any model that combines molecular mechanics and Poisson-Boltzmann solvation energies.