Author
Keywords
Abstract

An efficient method for calculating the free energy of solvation of a (macro)molecule embedded in a continuum solvent is presented. It is based on the fully analytical evaluation of the volume and spatial symmetry of the solvent that is displaced from around a solute atom by its neighboring atoms. The two measures of solvent displacement are combined in empirical equations to approximate the atomic (or self) electrostatic solvation energy and the solvent accessible surface area. The former directly yields the effective Born radius, which is used in the generalized Born (GB) formula to calculate the solvent-screened electrostatic interaction energy. A comparison with finite-difference Poisson data shows that atomic solvation energies, pair interaction energies, and their sums are evaluated with a precision comparable to the most accurate GB implementations. Furthermore, solvation energies of a large set of protein conformations have an error of only 1.5%. The solvent accessible surface area is used to approximate the nonpolar contribution to solvation. The empirical approach, called FACTS (Fast Analytical Continuum Treatment of Solvation), is only four times slower than using the vacuum energy in molecular dynamics simulations of proteins. Notably, the folded state of structured peptides and proteins is stable at room temperature in 100-ns molecular dynamics simulations using FACTS and the CHARMM force field.

Year of Publication
2008
Journal
Journal of Computational Chemistry
Volume
29
Issue
5
Number of Pages
701-715
Date Published
2008 Apr 15
Type of Article
Research Article
ISSN Number
1096-987X
DOI
10.1002/jcc.20832
Alternate Journal
J. Comput. Chem.
PMID
17918282
Download citation