Combining implicit solvation models with hybrid quantum mechanical/molecular mechanical methods: A critical test with glycine

Abstract

A combined approach to study reactions in solution in which the solute and a number of solvent molecules are described with a hybrid quantum mechanical/molecular mechanical (QM/MM) method, and the bulk solvent is represented by a polarizable continuum model (PCM) has been implemented. In this way, both short-range effects of the first-solvation shell and long-range electrostatics due to the bulk solvent can be taken into account. By carefully choosing the size of the solute–solvent cluster and the QM/MM partition, the current QM/MM/PCM approach can offer both computational efficiency and accuracy. The approach has been illustrated by two simple systems: water-dimer and glycine in water. The results demonstrated that the current approach offers a satisfactory description of solvation effects on the geometry and energetics of neutral and charged hydrogen-bonding systems. The method correctly produced the relative stability of the zwitterionic and neutral forms of glycine in solution, which was found to be a subtle issue in previous studies. The approach can be extended to study reactions in biomolecules in which part of the system is treated with QM/MM, and the bulk solvent plus part of the protein or nucleic acids are described with either a continuum or approximate microscopic representation.