Hybrid ab initio QM/MM simulation of N-methylacetamide in aqueous solution

Combined quantum mechanical and molecular mechanical (QM/MM) simulations of N-methylacetamide in aqueous solution have been carried out to investigate the charge polarization of the solute and to explore the feasibility of hybrid QM/MM calculations using ab initio methods. In the present study, the ab initio Hartree-Fock theory along with the 3-21G basis set was used in the quantum mechanical calculations. Statistical mechanical Monte Carlo approach was then applied in molecular mechanical simulations, employing the empirical TIP3P model for water. Comparisons with results obtained from the hybrid semiempirical Austin model 1 (AM1)/TIP3P and Jorgensen's OPLS (optimized potential for liquid simulations) potential were made, and a good accord among the three methods has been obtained. The solute charge polarization was analyzed through population analyses and determination of polarization energies. We found that the polarization effects contribute 10-15% to the total solute-solvent interaction energy for N-methylacetamide in water.