The MOD-QM/MM Method

Abstract

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.

Locating Minimum Energy Crossings of Different Spin States Using the Fragment Molecular Orbital Method

“…For example, the solvated metalloproteins are usually reduced to the active site models embedded in polarizable medium. ,,, For accurate description of the ISC kinetics in large biological systems, it is important to account for the influence of the protein chains and the surrounding water molecules on the active site, which is too expensive with the conventional electronic structure methods and requires alternatives. The hybrid quantum mechanics/molecular mechanics (QM/MM) method in which a small part of the system is described with QM, while the surrounding protein chains and the solvent molecules are treated with MM, is one of such alternatives. − The main QM/MM challenge is the accurate description of the interaction between the QM and MM regions . In contrast, the fragment-based fully QM methods offer a uniform quantum description of the entire system, which is a more universal and potentially more accurate approach …”