Due to the high computational costs of explicit solvent simulations, the development of accurate implicit solvent models is an attractive approach to reach longer timescales in biomolecular simulations. Possibly the most crucial aspect an implicit solvent model is the calculation of the electrostatic solvation energy. To completely describe the electrostatic solvation energy the response of the solvent to the solute and vice versa should be considered, but in empirical force-field calculations the solute charge response to the solvent is not considered. The benchmark of continuum electrostatic calculations is the Poisson-Boltzmann (PB) equation, where a finite difference approach is used to solve for the potential. This method, although accurate, is computationally demanding and does not lend itself to energy minimization or dynamics because the forces cannot be calculated analytically. Recent development of the generalized born approach, a pairwise-approximation to the PB method, has been shown to reproduce remarkably well the PB electrostatic solvation energy if one uses the same definition for the molecular volume. In 2002 Lee et. al. developed new grid-based and analytical born models that empirically correct for the non-spherical nature of the molecular volume. These models were shown to have excellent agreement with PB calculations. In 2003 an extension to the previous work of Lee et. al. refined their empirical correction for the molecular volume, and included a vector based scaling approach to correct error in the standard overlapping atomic functions approach. They also developed an accurate solvent-accessible surface area approximation to account for the nonpolar contribution to the solvation energy that is based on the same computational machinery as their GB model. This recent method by Lee et. al. has been shown to be one of the most accurate GB models to date.
Lee, Salsbury and Brooks, J. Chem. Phys. 116: 10606-10614 (2002)
Lee, Feig, Salsbury and Brooks, J. Comput. Chem 24:1348-1356 (2003)
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04-20-2009 9:54 AM
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Jason