We here suggest and test a new method to obtain stable energies in proteins for charge-neutral reactions by running large quantum mechanical (QM) calculations on structures obtained by combined QM and molecular mechanics (QM/MM) geometry optimization on several snapshots from molecular dynamics simulations. As a test case, we use a proton transfer between a metal-bound cysteine residue and a se...

Lately, there has been great interest in performing free-energy perturbation (FEP) at the combined quantum mechanics and molecular mechanics (QM/MM) level, e.g. for enzyme reactions. Such calculations require extensive sampling of phase space, which typically is prohibitive with density-functional theory or ab initio methods. Therefore, such calculations have mostly been performed with semiempi...

We present a novel quantum mechanical/molecular mechanics (QM/MM) approach in which a quantum subsystem is coupled to a classical subsystem described by the AMOEBA polarizable force field. Our approach permits mutual polarization between the QM and MM subsystems, effected through multipolar electrostatics. Self-consistency is achieved for both the QM and MM subsystems through a total energy min...

In this paper we identify the superposition principle as a main source of problems in QM (measurement, collapse, non-locality etc.). Here the superposition principle for individual systems is substituted by the antisuperposition principle: no non-trivial superposition of states is a possible individual state (for ensembles the superposition principle is true). The modified QM is based on the an...

We present an ab initio polarizable representation of classical molecular mechanics (MM) atoms by employing an angular momentum-based expansion scheme of the point charges into partial wave orbitals. The charge density represented by these orbitals can be fully polarized, and for hybrid quantum-mechanical-molecular-mechanical (QM/MM) calculations, mutual polarization within the QM/MM Hamiltonia...

A new multiscale computational methodology was developed to effectively incorporate the scattered electric field of a plasmonic nanoparticle into a quantum mechanical (QM) optical property calculation for a nearby dye molecule. For a given location of the dye molecule with respect to the nanoparticle, a frequency-dependent scattering response function was first determined by the classical elect...

Combined quantum-mechanics/molecular-mechanics (QM/MM) methods are making rapid progress both methodologically and with respect to their range of application. Mechanistic studies on enzymes, including contributions towards the understanding of enzyme catalysis, continue to be a major target. They are joined by calculations of pK(a) values, redox properties, ground- and excited-state spectroscop...

Structural and energetic changes are two important characteristic properties of a chemical reaction process. In the condensed phase, studying these two properties is very challenging because of the great computational cost associated with the quantum mechanical calculations and phase space sampling. Although the combined quantum mechanics/molecular mechanics (QM/MM) approach significantly reduc...

Hybrid QM/MM methods combine the rigor of quantum mechanical (QM) calculations with the low computational cost of empirical molecular mechanical (MM) treatment allowing to capture dynamic properties to probe critical atomistic details of enzyme reactions. Catalysis by RNA enzymes (ribozymes) has only recently begun to be addressed with QM/MM approaches and is thus still a field under developmen...

This paper presents a theoretical and empirical analysis of the implications of a quality management QM initiative on strategic flexibility. Our study defines flexibility from a strategic approach and examines the extent to which, why, and how the triggering factors of strategic flexibility are related to QM elements. The hypotheses put forward are tested in an empirical study carried out on a ...