Parameters, molecular mechanics,

I ll e con cept of a param cter set is an iin port an t (but often in con vc-nicnl) aspect of molecular m cchan ics calculation s. Molecular m ech an ics tries (o use experirn cn la I data to replace a priori com pu-tation, but in m an y situation s the experirn en tal data is n ot kn own and a parameter is missing. Collecting parameters, verification of their validity, and the relation ship of these molecular mechanics parameters to chemical and structural moieties are all important an d difficult topics. 

The entries in molecular mechanics parameter files are described in th e /lypcrChem iicfcre.nce Manual. Tfse th e folio won g proced ii re to modify an existing parameter set ... 

Delpeyroux and coworkers16 have developed a set of molecular mechanics parameters for nitramines (R—N—NO2) for the EMO program and used it in conjunction with MM2-85 parameters to calculate the structures of 1,4-dinitro-glycoluryl (8), 1,3-dinitro-4,6-diacetylglycoluryl (9) and 2,5,7,9-tetranitro-tetraazabicyclo(4.3.0)nonanone (10). The complete parameter list for the nitramine functionality is provided in Reference 16 but the parameterization procedure is not discussed. 

X-ray structural data for [Ru(bpy)3] " " and a wide range of other polypyridyl derivatives of Ru have been used to develop molecular mechanics parameters for these types of complex with the MM3 force field. Correlations between coordination geometry and emission properties of the Ru complexes have been examined. 

Molecular mechanics (also known as force field calculations)261 is a method for the calculation of conformational geometries.262 It is used to calculate bond angles and distances, as well as total potential energies, for each conformation of a molecule.263 Molecular orbital calculations (p. 28) can also give such information, but molecular mechanics is generally easier, cheaper (requires less computer time), and/or more accurate. In mo calculations, positions of the nuclei of the atoms are assumed, and the wave equations take account only of the electrons. Molecular mechanics calculations ignore the electrons, and study only the positions of the nuclei. Another important difference is that in an mo calculation each molecule is treated individually, but in molecular mechanics, parameters are obtained for small, simple molecules and then used in the calculations for larger or more complicated ones. 

The simple harmonic terms used to represent the energy of bond stretching in typical protein molecular mechanics force fields cannot model the making and breaking of chemical bonds. Also, molecular mechanics parameters are usually developed based on the properties of stable molecules, and so might not be applicable to transition states and intermediates. Molecular mechanics functions and parameters can be developed specifically for reactions, an approach that has been... 

S. Grigoras and T. H. Lane,/. Comput. Chem., 9, 25 (1988). Molecular Mechanics Parameters for Organosilicon Compounds Calculated from Ab Initio Computations. 

This volume has two appendices. The first is a compilation by Professors Fiji Osawa and Kenny B. Lipkowitz of published molecular mechanics parameters. All too frequently, it seems, a program employing an empirical force field chokes on a structure for which it has no parameters. The tabulation in Appendix 1 will help users of molecular mechanics and molecular dynamics programs track down supplemental parameters required for their calculations. 

Using Ab Initio Calculations to Develop Molecular Mechanics Parameters for Use in Biological Simulations. ... 

In summary, quantum mechanics attempts to model the position or distribution of the electrons or bonds, while mtv lecular mechanics attempts to model the positions of the nuclei or atoms. Quantum mechanics calculations are used commonly to generate or verify molecular mechanics parameters. Larger. structures can be studied hy use of molecular mechanics, and with. simulation techniques such as molecular dynamics, the behavior of drugs in solution or even in pas.sage through bilayer membranes can he studied. 

Blair, J.T., Levy, R.M. and Krogh-Jespersen, K. (1990) Molecular Mechanics Parameters for Electronically Excited States The (n,tr ) Singlet State of Formaldehyde, Chem. Phys. Letts. 166, 429—436. 

Ab initio calculations for activated complex molecular mechanics parameters reported in paper No additional parameters necesary... 

A united atom molecular mechanics parameter set for pyranoses has been developed from ab initio molecular orbital calculations and used to compute anomeric free energies for a series of simple monosaccharides in water. An empirical method has been employed to predict the magnitudes and signs of two-bond spin coupling constants in aldopyranosyl rings. Although designed... 

AUinger Nl, Zhou X, Bergsma 1 (1994) Molecular mechanics parameters. J Mol Struct Theochem 312 69-83... 

Since the symbolism in common usage does not usually differentiate which of these quantities is under discussion, the reader must always keep in mind whether molecular mechanics parameters, or force constants, are being discussed. In the past, much confusion has resulted in the literature from the fact that authors do not commonly differentiate these two cases. They know which one they are discussing, and they assume that the reader will also know what they are discussing. 

McKean s Eq. (6.1) is expected to (and does) work well in the absence of serious differences in the steric and electrostatic effects exerted upon the bonds in question. By substituting the molecular mechanics parameter (k) for the actual bond length (ro), Eq. (6.3) can be used in a general way with a molecular mechanics force field. To this end, one also needs to use Eq. (6.3) to determine the force parameter (k,) for the bond under examination, and that replaces the ordinary force constant. The rest of the force field will take care of any unusual steric or electrostatic effects. 

Since it is a non-quantum mechanical method, molecular mechanics is not intrinsically well suited to treating reaction mechanisms other than "reactions" that are simply conformational changes. That is, it would be completely unreasonable to study a bond-breaking process using a standard molecular mechanics package, because the method was not at all parameterized to treat bond-broken structures. Similarly, we might expect that an insufficient data base would exist to allow the development of reliable molecular mechanics parameters for reactive intermediates. Nevertheless, in some specific cases the method has been applied successfully to the evaluation of reaction mechanisms. 

Park S, Radmer RJ, Klein TE, Pande VS (2005) A new set of molecular mechanics parameters for hydroxyproline and its use in molecular dynamics simulations of coUagen-like peptides. J Comput Chem 26 1612-1616... 

The following contains portions of molecular data files generated by Insightll/discover for the various systems considered in this chapter. Only nonstandard residues are included. Molecular mechanics parameters for the standard residues are given in Reference [30]. In particular ... 

Song, K., Hornak, V., de los Santos, C., Grollman, A. P., Simmerling, C. (2008). Molecular mechanics parameters for the FapydG DNA lesion. Journal of Computational Chemistry, 29,17. 

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