Interfacing Q‐Chem and CHARMM to perform QM/MM reaction path calculations

Abstract

A hybrid quantum mechanical/molecular mechanical (QM/MM) potential energy function with Hartree‐Fock, density functional theory (DFT), and post‐HF (RIMP2, MP2, CCSD) capability has been implemented in the CHARMM and Q‐Chem software packages. In addition, we have modified CHARMM and Q‐Chem to take advantage of the newly introduced replica path and the nudged elastic band methods, which are powerful techniques for studying reaction pathways in a highly parallel (i.e., parallel/parallel) fashion, with each pathway point being distributed to a different node of a large cluster. To test our implementation, a series of systems were studied and comparisons were made to both full QM calculations and previous QM/MM studies and experiments. For instance, the differences between HF, DFT, MP2, and CCSD QM/MM calculations of H2O···H2O, H2O···Na+, and H2O···Cl− complexes have been explored. Furthermore, the recently implemented polarizable Drude water model was used to make comparisons to the popular TIP3P and TIP4P water models for doing QM/MM calculations. We have also computed the energetic profile of the chorismate mutase catalyzed Claisen rearrangement at various QM/MM levels of theory and have compared the results with previous studies. Our best estimate for the activation energy is 8.20 kcal/mol and for the reaction energy is −23.1 kcal/mol, both calculated at the MP2/6‐31+G(d)//MP2/6‐31+G(d)/C22 level of theory. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007