Molecular mechanics generalized

CHARMM (Chemistry at HARvard Molecular Mechanics) General-purpose... 

Some General Features of Molecular Mechanics Force Fields... 

Molecular mechanics methods are not generally applicable to structures very far from equilibrium, such as transition structures. Calculations that use algebraic expressions to describe the reaction path and transition structure are usually semiclassical algorithms. These calculations use an energy expression fitted to an ah initio potential energy surface for that exact reaction, rather than using the same parameters for every molecule. Semiclassical calculations are discussed further in Chapter 19. 

For ah initio, semiempirical, or molecular dynamics calculations, the amount of CPU time necessary is generally the factor of greatest concern to researchers. For very large molecules, memory use is of concern for molecular mechanics... 

Organic molecules are generally composed of covalent bonded atoms with several well-defined hybridization states tending to have well-understood preferred geometries. This makes them an ideal case for molecular mechanics parameterization. Likewise, organic molecules are the ideal case for semiempirical parameterization. 

The ability to perform molecular orbital (MO) calculations on metals is extremely useful because molecular mechanics methods are generally unable to treat metals. This is because metals have a wide range of valences, oxidation states, spin multiplicities, and have unusual bonding situations (e.g., dtt-pjt back bonding). In addition, the nondirectional nature of metallic bonding is less amenable to a ball and spring interpretation. 

Quantum mechanical calculations generally have only one carbon atom type, compared with the many types of carbon atoms associated with a molecular mechanics force field like AMBER. Therefore, the number of quantum mechanics parameters needed for all possible molecules is much smaller. In principle, very accurate quantum mechanical calculations need no parameters at all, except fundamental constants such as the speed of light, etc. 

Modem cancer therapy has been primarily dependent upon surgery, radiotherapy, chemotherapy, and hormonal therapy (72) (see Chemotherapeutics,anticancer Hormones Radiopharmaceuticals). Chemotherapeutic agents maybe able to retard the rate of growth, but are unable to eradicate the entire population of neoplastic cells without significant destmction of normal host tissue. This serious side effect limits general use. More recentiy, the immunotherapeutic approach to cancer has involved modification and exploitation of the cellular and molecular mechanisms in host defense, regulation of tissue proliferation, tissue differentiation, and tissue survival. The results have been more than encouraging. 

M. J. Halsey, R. A. Miller, and J. A. Sutton, Molecular Mechanisms in General Anesthesia, ChurchiU Livingston, Edinburgh, Scodand, 1974. 

Computer simulations of electron transfer proteins often entail a variety of calculation techniques electronic structure calculations, molecular mechanics, and electrostatic calculations. In this section, general considerations for calculations of metalloproteins are outlined in subsequent sections, details for studying specific redox properties are given. Quantum chemistry electronic structure calculations of the redox site are important in the calculation of the energetics of the redox site and in obtaining parameters and are discussed in Sections III.A and III.B. Both molecular mechanics and electrostatic calculations of the protein are important in understanding the outer shell energetics and are discussed in Section III.C, with a focus on molecular mechanics. 

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