Calculation of the aqueous solvation energy and entropy, as well as free energy, of simple polar solutes

With the advent of more powerful computers, the question of calculating thermodynamic quantities, such as the energy and the entropy, in solute-solvent systems is revisited. The calculation of these thermodynamic quantitites was limited in the past by their slow convergence relative to the free energy. Using molecular dynamics simulations, the energy, entropy, and free energy of solvation of NMA and CH(3)NH(2), as well as their relative values, have been determined. Three different methods (the thermodynamic perturbation method, the thermodynamic integration method, and a finite-difference method) are compared. The finite difference method gives the best results and accurate values for the entropy and energy were obtained using a reasonable amount to computer time. The results suggest that a meaningful thermodynamic description of biomolecular processes can be realized with present methods and the available computer time.