Estimating entropies from molecular dynamics simulations

The methods to compute the excess entropy and the entropy of solvation using liquid water as a test system were studied. The accuracy and convergence behavior of five methods based on thermodynamic integration and perturbation techniques was evaluated. Through the thermodynamic integration accurate entropy differences were obtained in which many copies of a solute were desolvated. Only two methods yield useful results, the calculation of solute-solvent entropy through thermodynamic integration and the calculation of solvation entropy through the temperature derivative of the corresponding free-energy difference, when one solute molecule is involved.