The CHARMM–TURBOMOLE Interface for Efficient and Accurate QM/MM Molecular Dynamics, Free Energies, and Excited State Properties

The QM/MM interface between CHARMM and TURBOMOLE is described. CHARMM provides an extensive set of simulation algorithms, like molecular dynamics (MD) and free energy perturbation, and support for mature non-polarizable and Drude polarizable force fields. TURBOMOLE provides fast QM calculations using DFT or wave function methods and excited state properties. CHARMM–TURBOMOLE is well-suited for ex-tended QM/MM MD simulations using first principles methods with large (triple-ζ) basis sets. We demonstrate these capabilities with a QM/MM simulation of Mg2+(aq), where the MM outer sphere water molecules are represented using the SWM4-NDP Drude polarizable force field and the ion and inner coordination sphere are represented using QM PBE, PBE0, and MP2 methods. The relative solvation free energies of Mg2+ and Zn2+ were calculated using thermodynamic integration. We also demonstrate the features for excited state properties. We calculate the time-averaged solution absorp-tion spectrum of indole, the emission spectrum of the indole 1La excited state, and the electronic circular dichroism spectrum of an oxacepham