Advances in implicit models of water solvent to compute conformational free energy and molecular dynamics of proteins at constant pH.

Modern implicit solvent models for macromolecular simulations in water-proton bath are considered. The fundamental quantity that implicit models approximate is the solute potential of mean force, which is obtained by averaging over solvent degrees of freedom. The implicit solvent models suggest practical ways to calculate free energies of macromolecular conformations taking into account equilibrium interactions with water solvent and proton bath, while the explicit solvent approach is unable to do that due to the need to account for a large number of solvent degrees of freedom. The most advanced realizations of the implicit continuum models by different research groups are discussed, their accuracy are examined, and some applications of the implicit solvent models to macromolecular modeling, such as free energy calculations, protein folding, and constant pH molecular dynamics are highlighted.

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