Abstract
Based on recent developments in generalized Born (GB) theory that employ rapid volume integration schemes (M. S. Lee, F. R. Salabury, Jr., and C. L. Brooks III, J Chem Phys 2002, 116, 10606) we have recast the calculation of the self‐electrostatic solvation energy to utilize a simple smoothing function at the dielectric boundary. The present GB model is formulated in this manner to provide consistency with the Poisson–Boltzmann (PB) theory previously developed to yield numerically stable electrostatic solvation forces based on finite‐difference methods (W. Im, D. Beglov, and B. Roux, Comp Phys Commun 1998, 111, 59). Our comparisons show that the present GB model is indeed an efficient and accurate approach to reproduce corresponding PB solvation energies and forces. With only two adjustable parameters—a~0~ to modulate the Coulomb field term, and a~1~ to include a correction term beyond Coulomb field—the PB solvation energies are reproduced within 1% error on average for a variety of proteins. Detailed analysis shows that the PB energy can be reproduced within 2% absolute error with a confidence of about 95%. In addition, the solvent‐exposed surface area of a biomolecule, as commonly used in calculations of the nonpolar solvation energy, can be calculated accurately and efficiently using the simple smoothing function and the volume integration method. Our implicit solvent GB calculations are about 4.5 times slower than the corresponding vacuum calculations. Using the simple smoothing function makes the present GB model roughly three times faster than GB models, which attempt to mimic the Lee–Richards molecular volume. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 1691–1702, 2003