Combined QM/MM methods for the simulation of condensed phase processes using an approximate DFT approach

Abstract

The realistic simulation of chemical processes occurring in solution and in the active sites of biomolecules is a major challenge for theoretical chemistry since the requirement for a high (chemical) accuracy collides with the large system sizes and long timescales involved. In the last years much effort has been invested into the development of theoretical approaches that allow (i) the treatment of systems of large size with sufficient accuracy and (ii) the simulation of longer timescales. In this chapter, we discuss several choices to construct molecular models and the corresponding theoretical methods. This concerns in particular the recent development of multi-scale methods, where the approximate quantum mechanical (QM) method SCC-DFTB is coupled with molecular mechanics (MM) force fields and continuum electrostatic methods (CM) into combined QM/MM and QM/MM/CM approaches. Chemical events occurring on long timescales are approached by using either direct molecular dynamics simulations, minimum energy pathways based on geometry optimizations or free energy methods, where the potential of mean force along selected coordinate(s) is calculated. Various possible system setups and simulation methods are discussed for the investigation of the structure and energetics of polypeptides in the gas phase and solution as well as proton-transfer reactions in complex environments.