Molecular mechanics computational portion

This is clearly a more complex reaction than that of HKMT just described. Of the seven steps shown in the movie all but one involve conformational changes of the enzyme that are more in the domain of Molecular Mechanics than in that of quantum chemistry (we are studying these conformational steps, but they are not the topic of the present chapter). The sole exception is step 4, catalytic incorporation, which actually involves a multistep mechanism of chemical reactions. This is where theory and computation have to step in to help elucidate the mechanism. The first steps of the process involve the construction of cluster models for the calculation of relevant portions of the potential energy surface corresponding to proposed reaction steps. Several key choices have to be made for which reactions to consider. 

As far as large, complex, and flexible molecular systems are considered, an effective computational treatment is represented by the use of a hybrid QM/MM methodology that allows us to combine two or more computational methods for different portions of the system in such a way that only the chemical and physical interesting region is modeled at the highest level of accuracy. As an example, the well-known ONIOM [72-74] scheme allows the combination of a variety of quantum mechanical, semiempirical, and molecular mechanics methods, providing an accurate and well-defined Hamiltonian. 

A fourth approach utihzes ONIOM, a computational method devised by Morokuma. The method was intended to dissect a large molecule into portions. One portion is subject to quantum mechanical computation. Further portions are treated by molecular mechanics. In dissecting a molecule by breaking bonds, the Morokuma method caps the dangling valences with light atoms as hydrogens. 

The algorithms of the mixed classical-quantum model used in HyperChem are different for semi-empirical and ab mi/io methods. The semi-empirical methods in HyperChem treat boundary atoms (atoms that are used to terminate a subset quantum mechanical region inside a single molecule) as specially parameterized pseudofluorine atoms. However, HyperChem will not carry on mixed model calculations, using ab initio quantum mechanical methods, if there are any boundary atoms in the molecular system. Thus, if you would like to compute a wavefunction for only a portion of a molecular system using ab initio methods, you must select single or multiple isolated molecules as your selected quantum mechanical region, without any boundary atoms. 

The use of radial distribution functions is one of the costs paid by simulations methods to the high computational cost of this approach. The ever increasing availability of computer power has allowed a sizable portion of these shortcomings to be eliminated. In a few years the description of the QM part of QM/MM applications has progressed from a rather crude semiempirical description to ab initio levels now sufficiently accurate to describe with reasonable accuracy solvent effects on molecular properties and reaction mechanisms. A greater availability of computer power has also permitted the introduction of some improvements in the formulation of the site-site potentials we briefly characterized above. 

The computation of internal state densities and partition functions for polyatomic molecules is an essential task in the theoretical treatment of molecular gases. A first principles approach to the statistical thermodynamics of polyatomic gases requires the computation of the internal molecular energy levels based on an ab initio quantum mechanical (QM) determination of portions of the potential energy surface. Likewise, statistical theories of chemical reactions, such as Rice-Ramsberger-KasseUMarcus (RRKM) theory or transition state... 

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