Molecular mechanics parametrization

Molecular mechanics calculations don t explicitly treat the electrons in a molecular system. Instead, they perform computations based upon the interactions among the nuclei. Electronic effects are implicitly included in force fields through parametrization. 

Fernandez, B., M. A. Rios, and L. Carballeira. 1991. Molecular Mechanics (MM2) and Conformational Analysis of Compounds with N-C-O Units. Parametrization of the Force Field and Anomeric Effect. J. Comput. Chem. 12, 78-90. 

Dynamic NMR gives information on the number and symmetries of conformations present in solution and on the energy barriers separating these conformations. This is particularly true for systems with barriers between about 25 and 90 kJ mol-1, a situation which often occurs in the medium ring. The interpretation of the NMR data can be carried out by the examination of molecular models, but this is a relatively crude and sometimes misleading method. Empirical force field (or molecular mechanics) calculations are much superior, even though the parametrization of heteroatoms may be open to question. Quantum mechanical calculations are not very suitable the semiempirical type, e.g. MINDO, do not reproduce conformational properties of even cyclohexane satisfactorily, and the ab initio... 

The molecular mechanics force field MM3 is better parametrized for carbohydrates (89JA8551, 90JA8551, 90JA8293, 92CAR(244)49). 

In Fig. 1 we show the correlation between E and experimental heats of formation for the (complete) set of C22H14 benzenoid isomers. For comparison we also present some recent data for the same set of compounds, obtained by a semiempirical MNDO method [21] and by the MMX/PI version of molecular mechanics calculations [22], The only conclusion we wish to draw from Fig. 1 is that HMO theory is capable of reproducing the experimental enthalpies of benzenoid hydrocarbons with an accuracy which is not much worse than that of the much more sophisticated (and highly parametrized) molecular orbital and molecular mechanics approaches. 

Method (III) attempts to include a discrete molecular description of the solvent structure around a central solute molecule. The solute molecule is described, again, through a QM calculation while the spatial distribution, charge distribution, polarizabilities etc. of the adjacent part of the solvent is represented by a parametrized molecular mechanics (MM) model. The parametrization may be achieved through high level calculations on the isolated solvent molecules. 

Once the gas phase Hamiltonian is parametrized as a function of the inner-sphere reaetion coordinate(s), the free energy is calculated as a function of the proton coordinate(s), the scalar solvent coordinates, and the inner-sphere reaction coordinate(s). Note that this approaeh assumes that the optimized geometries of the VB states are not significantly affected by the solvent. For proton transfer reactions, the proton donor-acceptor distance may be treated as an additional solute reaction coordinate that ean be incorporated into the molecular mechanical terms describing the diagonal matrix elements hf- and, in some cases, the off-diagonal matrix elements (/io)y. If the inner-sphere reaction coordinate represents a slow mode, it is treated in the same way as the solvent coordinates. As discussed throughout the literature, however, often the inner-sphere reaction coordinate must be treated quantum mechanically [27, 28]. In this case, the inner-sphere reaction coordinate is treated in the same way as the proton coordinate(s), and the vibrational wave functions depend explicitly on both the proton coordinate(s) and the inner-sphere reaction coordinate(s). 

Some theoretical purists tend to view molecular mechanics calculations as merely a collection of empirical equations or as an interpolative recipe that has very little theoretical Justification. It should be understood, however, that molecular mechanics is not an ad hoc approach. As previously described, the Born-Oppenheimer approximation allows the division of the Schrodinger equation into electronic and nuclear parts, which allows one to study the motions of electrons and nuclei independently. From the molecular mechanics perspective, the positions of the nuclei are solved explicitly via Eq. (2). Whereas in quantum mechanics one solves, which describes the electronic behavior, in molecular mechanics one explicitly focuses on the various atomic interactions. The electronic system is implicitly taken into account through judicious parametrization of the carefully selected potential energy functions. 

Theoretical Methods for the Liquid. The approaches to be described all attempt to calculate the response functions for a central water molecule influenced by the surrounding medium. The older methods represent the surrounding medium through a continuum parametrized by a dielectric function but more recently the medium has been described by molecular mechanics (MM). In both cases the central molecule is the subject of a full correlated quantum mechanical treatment. 

A step forward along the route to the correct modelling of the spectroscopy and photochemical reactivity of photoreactive proteins is represented by the implementation of a Quantum Mechanics/Molecular Mechanics (QM/MM) computational strategy based on a suitable QM part coupled with a protein force field such as AMBER [34] (or CHARMM [35]). Very recently a CASPT2//CASSCF/AMBER method for rhodopsin has been implemented in our laboratory [36,37] within the QM/MM hnk-atom scheme [38]. Special care has been taken in the parametrization of the protonated Schiff base linkage region that describes the dehcate border region between the MM (the protein)... 

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