Implicit solvent models

Implicit solvent models for biomolecular simulations are reviewed and their underlying statistical mechanical basis is discussed. The fundamental quan tity that implicit models seek to approximate is the solute potential of me an force, which determines the statistical weight of solute conformations, and which is obtained by averaging over the solvent degrees of freedom. It is possible to express the total free energy as the reversible work perform ed in two successive steps. First, the solute is inserted in the solvent wi th zero atomic partial charges; second, the atomic partial charges of the s olute are switched from zero to their full values. Consequently, the total solvation free energy corresponds to a sum of non-polar and electrostatic c ontributions. These mio contributions are often approximated by simple geom etrical models (such as solvent exposed area models) and by macroscopic con tinuum electrostatics, respectively. One powerful route is to approximate t he average solvent density distribution around the solute, i.e. the solute- solvent density correlation functions, as in statistical mechanical integra l equations. Recent progress with semi-analytical approximations makes cont inuum electrostatics treatments very efficient, Still more efficient are fu lly empirical, knowledge-based models, whose relation to explicit solvent t reatments is not fully resolved, however. Continuum models that treat both solute and solvent as dielectric continua are also discussed, and the relat ion between the solute fluctuations and its macroscopic dielectric constant (s) clarified. (C) 1999 Elsevier Science B.V. All rights reserved.