The MOD-QM/MM Method: Applications to Studies of Photosystem II and DNA G-Quadruplexes.

Quantum mechanics/molecular mechanics (QM/MM) hybrid methods are currently the most powerful computational tools for studies of structure/function relations and catalytic sites embedded in macrobiomolecules (eg, proteins and nucleic acids). QM/MM methodologies are highly efficient since they implement quantum chemistry methods for modeling only the portion of the system involving bond-breaking/forming processes (QM layer), as influenced by the surrounding molecular environment described in terms of molecular mechanics force fields (MM layer). Some of the limitations of QM/MM methods when polarization effects are not explicitly considered include the approximate treatment of electrostatic interactions between QM and MM layers. Here, we review recent advances in the development of computational protocols that allow for rigorous modeling of electrostatic interactions in biomacromolecules and structural refinement, beyond the common limitations of QM/MM hybrid methods. We focus on photosystem II (PSII) with emphasis on the description of the oxygen-evolving complex (OEC) and its high-resolution extended X-ray absorption fine structure spectra (EXAFS) in conjunction with Monte Carlo structural refinement. Furthermore, we review QM/MM structural refinement studies of DNA G4 quadruplexes with embedded monovalent cations and direct comparisons to NMR data.

A transferable H2O interaction potential based on a single center multipole expansion: SCME.

A transferable potential energy function for describing the interaction between water molecules is presented. The electrostatic interaction is described rigorously using a multipole expansion. Only one expansion center is used per molecule to avoid the introduction of monopoles. This single center approach turns out to converge and give close agreement with ab initio calculations when carried out up to and including the hexadecapole. Both dipole and quadrupole polarizability are included. All parameters in the electrostatic interaction as well as the dispersion interaction are taken from ab initio calculations or experimental measurements of a single water molecule. The repulsive part of the interaction is parametrized to fit ab initio calculations of small water clusters and experimental measurements of ice Ih. The parametrized potential function was then used to simulate liquid water and the results agree well with experiment, even better than simulations using some of the point charge potentials fitted to liquid water. The evaluation of the new interaction potential for condensed phases is fast because point charges are not present and the interaction can, to a good approximation, be truncated at a finite range.