ABSOLUTE FREE-ENERGY OF SOLVATION FROM MONTE-CARLO SIMULATIONS USING COMBINED QUANTUM AND MOLECULAR MECHANICAL POTENTIALS

A new method for computing the absolute free energy of solvation using combined quantum mechanical (QM) and molecular mechanical (MM) potentials and the Monte Carlo method is presented. In this procedure, the Hamiltonian associated with the QM region is first annihilated to form a pure classical (empirical) potential. The free energy for the latter system can then be easily evaluated using traditional approaches. The method is illustrated by computing the solvation free energy of Cl- in water, treating the ion quantum mechanically during the free energy simulation. A good agreement was found between the calculated and experimental results.