Development of a perturbative approach for Monte Carlo simulations using a hybrid ab initio QM/MM method

We present the development and assessment on the accuracy of perturbative approach for Monte Carlo simulations using a hybrid ab initio quantum mechanical/molecular mechanics (QM/MM) potential. The central idea of this approach is that for most solvent moves, the changes in the solute wavefunction are small, thus one can use the perturbation theory to approximate the energy change without having to perform full quantum calculation at each Monte Carlo step. Consequently, the computational demand can be reduced by several orders of magnitude while maintaining a reasonable level of accuracy. This opens new possibilities for using more accurate levels of theory to describe both solute and solvent molecules in Monte Carlo simulations.