Incorporation of the TIP4P water model into a continuum solvent for computing solvation free energy

Abstract

The continuum solvent model is one of the commonly used strategies to compute solvation free energy especially for large-scale conformational transitions such as protein folding or to calculate the binding affinity of protein–protein/ligand interactions. However, the dielectric polarization for computing solvation free energy from the continuum solvent is different than that obtained from molecular dynamic simulations. To mimic the dielectric polarization surrounding a solute in molecular dynamic simulations, the first-shell water molecules was modeled using a charge distribution of TIP4P in a hard sphere; the time-averaged charge distribution from the first-shell water molecules were estimated based on the coordination number of the solute, and the orientation distribution of the first-shell waters and the intermediate water molecules were treated as that of a bulk solvent. Based on this strategy, an equation describing the solvation free energy of ions was derived.