Hybrid QM/MM approach

MD simulations require the description of the interactions between the particles (potential function, or a force field) of a molecular system [27]. The potential function can be defined on various levels. The most conunonly adopted potential functions in chemistry and biology are based on molecular mechanics (MM), with a classical treatment of particle-particle interactions. With well-chosen parameter sets, these potential functions can reproduce structural and conformational changes in systems, except chemical reactions. The analytic forms of the potential functions, which involve low computational cost, make it possible for MD simulations to include a huge number of atoms. When potentials based on quantum mechanics (QM) are adopted, MD simulations can give finer levels of detail, such as chemical reactions and electronic structures, but expensive computational costs are involved simultaneously. As a compromise, hybrid QM/MM approaches are... 

For organic force fields, as well as their extensions to transition metal compounds [180], ab-initio calculations are more and more often used. The validity of the quantum-mechanical method for the classes of compounds in question must be validated by comparison to experimental data. Calculated data are used as consistent reference data, or where experimental data are not available [181,182], as well as in the tuning of hybrid QM/MM approaches [183, 184]. 

These findings will be apphed for the future theoretical calculations of realistic large systems containing Ln atoms, for example, with the hybrid QM/MM approaches [86-88]. For such calculations, atoms or fragments in the nearby ligands around Ln must be treated as the QM region and... 

General physical principles of constructing hybrid QM/MM approaches state that the subsequent derivation of junction between quantum and classical subsystems requires a QM wave function underlying the MM description of PESs. This QM method is necessary, for example, to perform averaging of the effective Hamiltonian in Eq. (7). At the same time more important that this method should produce in a consistent manner one-electron states necessary for explicit formation of boundary and its response on the changes in molecular geometry of fragments and/or electronic structure of the i -subsystem. 

To go one step further into the modeling of decoherence for biological electron transfers, it is necessary to include the entire donor bridge acceptor (D-B-A) system and its environment in the computation. Although hybrid QM/MM approaches will clearly continue to be a key tool, special care needs be taken over the choice of the QM technique. In our group we have invested effort in the constrained DFT (cDFT) in the formalism introduced by Dederichs et al. and further developed by Wu and Van Voorhis based on optimized potential theory. 

In the present article, the absorption properties of the two native proteins, as well as the ESR and circular dichroism (CD) parameters, will be analyzed, at density functional theory (DFT) and time-dependent DFT (TD-DFT) level. The use of hybrid QM/MM approach will allow us to take into account the role of the macromolecular environment [32-37]. The evolution of the spectroscopic parameters with mutations will be also considered. The use of natural transition orbitals (NTOs) [26, 38] techniques will allow us to perform a systematic analysis of the nature and electronic properties of the excited states. 

The application of first-principles molecular dynamics to the study of organome-tallic systems or homogeneous catalytic processes in nmiaqueous solvents is certainly less extended than in water. Nevertheless, a survey of the literature shows that the number of AlMD-based studies in nonaqueous solvents is increasing. In many cases, due to the larger size of the complexes investigated and of the solvent molecules compared to in-water studies, the hybrid QM/MM approach is taken to simulate realistic model systems at a reduced computational cost. Simulations by means of first-principles molecular dynamics on ionic liquids [130] or frustrated Lewis pairs in organic solvents [131] are not covered here. 

Hofer TS, Hitzenberger M, Randolf BR (2012) Combining a dissociative water model with a hybrid QM/MM approach—a simulation strategy for the smdy of proton transfer reactions in solution. J Chem Theory Comput 8 3586... 

QM/MM calculation of the His-tagged peptide chelating with Ni ion. GAMESS/TINKER can perform the IMOMM scheme (Maseras and Morokuma 1995), which spearheads the entry of hybrid QM/MM approaches in computational transition metal chemistry. In the QM/MM calculation, the imidazoles on the side chain of the peptide and the metal ion with several neighboring water molecules are treated as a QM part calculated by GAMESS, and the remaining atoms are treated as a MM part calculated by TINKER. The IMQMM method is used to deal with the QM part with the transitional metal. 

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