Molecular mechanics studies

At any geometry g.], the gradient vector having components d EjJd Q. provides the forces (F. = -d Ej l d 2.) along each of the coordinates Q-. These forces are used in molecular dynamics simulations which solve the Newton F = ma equations and in molecular mechanics studies which are aimed at locating those geometries where the F vector vanishes (i.e. tire stable isomers and transition states discussed above). 

Most existing molecular mechanics studies of inorganic molecules required careful customization of force field parameters. 

Two successful and widespread appHcations of visualization techniques in the field of chemistry are the visualization of molecular orbitals and the visualization of molecules in molecular mechanics studies. 

Molecular mechanics is the simplest and the most commonly used molecular modelling technique. It focuses on the low energy structures of molecules which correspond to energy minima in the classical force field used to represent the molecule [44]. A typical molecular mechanics study consists of the following steps [45] ... 

Vibrational spectroscopy has played a very important role in the development of potential functions for molecular mechanics studies of proteins. Force constants which appear in the energy expressions are heavily parameterized from infrared and Raman studies of small model compounds. One approach to the interpretation of vibrational spectra for biopolymers has been a harmonic analysis whereby spectra are fit by geometry and/or force constant changes. There are a number of reasons for developing other approaches. The consistent force field (CFF) type potentials used in computer simulations are meant to model the motions of the atoms over a large ranee of conformations and, implicitly temperatures, without reparameterization. It is also desirable to develop a formalism for interpreting vibrational spectra which takes into account the variation in the conformations of the chromophore and surroundings which occur due to thermal motions. 

Stahl, M., Schopfer, U., Frenking, G., Hoffmann, R. W., 1997, Conformational Analysis with Carbon-Carbon Coupling Constants. A Density Functional and Molecular Mechanics Study , J. Org. Chem., 62, 3702. 

Quantum mechanical/molecular mechanical study on the Favorskii rearrangement in aqueous media has been carried out.39 The results obtained by QM/MM methods show that, of the two accepted mechanisms for Favorskii rearrangement, the semibenzilic acid mechanism (a) is favored over the cyclopropanone mechanism (b) for the a-chlorocyclobutanone system (Scheme 6.2). However, the study of the ring-size effects reveals that the cyclopropanone mechanism is the energetically preferred reactive channel for the a-chlorocyclohexanone ring, probably due to the straining effects on bicycle cyclopropanone, an intermediate that does not appear on the semibenzilic acid pathway. These results provide new information on the key factors responsible for the behavior of reactant systems embedded in aqueous media. 

A molecular mechanics study of TIPP and TIPPfT] produced about 70 structures within 3 kcal/mol of the lowest energy conformation in each... 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

Gresh N, Cisneros GA, Darden TA, Piquemal J-P (2007) Anisotropic, polarizable molecular mechanics studies of inter-, intra-molecular interactions, and ligand-macromolecule complexes. A bottom-up strategy. J Chem Theory Comput 3 1960... 

AB INITIO QUANTUM MECHANICAL/MOLECULAR MECHANICAL STUDIES OF HISTONE MODIFYING ENZYMES... 

Zhang Y, Kua J, McCammon JA (2003) Influence of structural fluctuation on enzyme reaction energy barriers in combined quantum mechanical/molecular mechanical studies. J Phys Chem B 107 ... 

Combined quantum mechanics/molecular mechanics studies have demonstrated that 7r-7r stacking interactions are important in determining the structural features of polyarene transition metal compounds such as the two ds Pd complexes.96... 

Barone, V., F. Fratemali, and P. L. Cristinziano. 1990. Sensitivity of Peptide Conformation to Methods and Geometrical Parameters. A Comparative Ab Initio and Molecular Mechanics Study of Oligomers of a-Aminoisobutyric Acid. Macromolecules 23, 2038-2044. 

Menziani, M.C., De Benedetti, P.G., Gago, F. and Richards, W.G. (1989) The binding of benzenesulfonamides to carbonic anhydrase enzyme. A molecular mechanics study and quantitative structure-activity... 

J. Pitarch, J. L. Pascual-Ahuir, E. Silla, I. Tunon, V. Moliner, Analysis of a Concerted Mechanism in /3-Lactam Enzymatic Hydrolysis. A Quantum Mechanics/Molecular Mechanics Study , J. Chem. Soc., Perkin Trans. 2, 1999, 1351-1356. 

Amara, P. V., Volbeda, A., Fontecilla-Camps, J. C. and Field, M. J. A. (1999) Hybrid density functional theory/molecular mechanics study of nickel-iron hydrogenase Investigation of the active site redox states./. Am. Chem. Soc., 121, 4468-77. 

With three linkage bonds as in the molecular mechanics study of the 1-6 disaccharide gentiobiose (12), the lowest 24 minima within 7 kcal mole which were reported did not include that observed in the crystal structure (20). Had the crystal structure conformation been one of the sets of starting parameters, it would have been included, but it is reasonable to assume that the conformational population in solution was also not fully represented. 

Previously, our molecular mechanics studies showed that the iduronate ring can adopt the (skew boat)... 

Synopsis of Stahl etal. (1991), Conformational Analysis with Carbon-Carbon Coupling Constants. A Density Functional and Molecular Mechanics Study . 

For a molecular mechanics study of this phenomenon, see DeTar Binzet Darba J. Org. Chem. 1987,52, 2074. These values arc from Strcilwiescr, Ref. I, p. 43, where values are also given for other conditions. Methyl bromide reacts faster than ethyl bromide (and in the case of 60% ethanol, ispropyl bromide) because most of it (probably all) reacts by the Sn2 mechanism. 

Sequences of sterically identical steps lead to isotacticity of the product. Active sites with two vacancies or with one vacancy and a loosely bound chlorine characteristic of p-TiCl3 with a chainlike structure are nonstereospecific and result in polymers with increased atacticity.306 Molecular mechanics studies on the basis of this model lent additional support for the asymmetric active center being responsible for stereoregulation.341 It was concluded that the main factor determining... 

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