Efficient computation of absolute free energies of binding by computer simulations. Application to the methane dimer in water

Abstract

An efficient procedure is noted for computing absolute free energies of binding for complexes in solution. Two series of computer simulations are required in which the substrate is annihilated in the solvent by itself and in the solvated complex. For illustration, the free energy of binding for two methane-like particles at their contact separation of 4 Å has been computed in TIP4P water. Though several alternatives are possible, in this case, Monte Carlo simulations were employed with statistical perturbation theory in the NPT ensemble at 25 °C and 1 atm. The results for the free energy of binding as well as for the potential of mean force are consistent with prior findings from the integral equation theory of Pratt and Chandler.