Molecular mechanics and dynamics

The GB equation is suitable for the description of solvent effects in molecular mechanics and dynamics [16], as well as in quantum mechanical calculations (17,18]. An excellent review of implicit solvation models, with more than 900 references, is given by Cramer and Truhlar [19]. 

W C, A Tempcz)rrk, R C Hawley and T Hendrickson 1990. Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. Journal of the American Chemical Society 112 6127-6129. ensson M, S Humbel, R D J Froese, T Matsubara, S Sieber and K Morokuma 1996. ONIOM A Multilayered Integrated MO + MM Method for Geometry Optimisations and Single Point Energy Predictions. A Test for Diels-Alder Reactions and Pt(P(t-Bu)3)2 + H2 Oxidative Addition. Journal of Physical Chemistry 100 19357-19363. 

The molecular mechanics force helds available are AMBER95 and CFIARMM. The molecular mechanics and dynamics portion of the code is capable of performing very sophisticated calculations. This is implemented through a large number of data hies used to hold different types of information along with keywords to create, use, process, and preprocess this information. This results in having a very hexible program, but it makes the input for simple calculations unnecessarily complex. QM/MM minimization and dynamics calculations are also possible. 

Still WC, Tempczyk A, Hawley RC, Hendrickson T (1990) Semianalytical treatment of salvation for molecular mechanics and dynamics. J Am Chem Soc 112 6127—6129. 

A chlorosulfolipid (224) has been isolated from the hepatopancreas of mussels from the northern Adriatic Sea. The structural determination, including the absolute stereochemistry, was carried out by extensive NMR spectral analysis and through molecular mechanics and dynamics calculations [229]. 

The probability distribution of isomeric conformations in PDMS is investigated by both conformational energy considerations and by molecular dynamics simulations. A comparatively smooth distribution of isomeric states is obtained from both approaches. A new RIS treatment, compatible with the molecular mechanics and dynamics considerations, is introduced for describing the conformational statistics of PDMS. 

Molecular mechanics and dynamics calculations have shown that the preorganization of 21 for cation or anion binding and recognition results from its high connectivity and its preformed cavity with converging binding sites and fairly fixed size [1.45,2.36b]. 

In this chapter we survey the molecular mechanics and dynamics studies of bioinorganic systems reported to date. We also address the problems involved in carrying out such studies and point to possible strategies for dealing with them. 

The solution structures of a number of metalloproteins with paramagnetic metal centers were determined with molecular mechanics and dynamics in combination with NMR spectroscopy (see also Chapter 9)1124-126,189]. Due to the complexity of the molecules, for metalloproteins a crystal structure of the compound or a derivative is often needed for the definition of the starting geometry. Molecular dynamics is then used to find low-eneigy conformers. The dynamics calculations also allow the visualization of areas of large flexibility, and this may lead to some understanding of the enzyme mechanism11891. 

Molecular mechanics and dynamics studies of metal-nucleotide and metal-DNA interactions to date have been limited almost exclusively to modeling the interactions involving platinum-based anticancer drugs. As with metal-amino-acid complexes, there have been surprisingly few molecular mechanics studies of simple metal-nucleotide complexes that provide a means of deriving reliable force field parameters. A study of bis(purine)diamine-platinum(II) complexes successfully reproduced the structures of such complexes and demonstrated how steric factors influenced the barriers to rotation about the Pt(II)-N(purine) coordinate bonds and interconversion of the head-to-head (HTH) to head-to-tail (HTT) isomers (Fig. 12.4)[2011. In the process, force field parameters for the Pt(II)/nucleotide interactions were developed. A promising new approach involving the use of ab-initio calculations to calculate force constants has been applied to the interaction between Pt(II) and adenine[202]. 

The AMBER-based approach used to model cyclic polyethers and cryptands has also been applied to the study of the Li+, Na+, and K+ complexes of three spherands (Fig. 14.3)12641. Experimentally determined metal ion selectivities were successfully reproduced. A similar AMBER-based model, used for molecular mechanics and dynamics of a cyclic urea-based spherand, was also successful in reproducing its metal ion selectivity12651. A number of new conformations of the spherand, including the global energy minimum, were located using molecular dynamics12651. 

Grootenhuis, P. D. J., Kollman, P. A. (1989), Molecular Mechanics and Dynamics Studies of Crown Ether-Cation Interactions Free Energy Calculations on the Cation Selectivity of Dibenzo-18-Crown-6 and Dibenzo-30-Crown-10, J. Am. Chem. Soc. Ill, 2152-2158. 

From sponges of the genus Jaspis collected at Fiji (300,301), Palau (300), and Papua New Guinea (302), jaspamide (jasplakinolide, 372) was isolated the compound shows potent insecticidal, antifungal, anthelminthic, and ichthyotoxic activity. The structure was determined by X-ray analysis (300). The solution conformation of372 was reported using NMR, molecular mechanics, and dynamics calculations (303). A complexation study was carried out with 372 and the univalent metal ions Li ", Na+, and K+. Li+ binding was observed, and the complex was characterized by NMR and molecular mechanics calculations (304). Jaspamide (372) has potent in... 

Fig. 1. Stereodrawing of the molecular structure of /V-pheynlacetyl-L-phenylalanine drawn by ORTEPll (Johnson, 1967). Molecular mechanics and dynamics calculations of the compound both in vacuum and in the crystal environment reproduced the observed crystal structure only when the appropriate partial electronic charges were used for the aromatic carbon and hydrogen atoms.

Molecular structure and shape are related to orbital angular momentum and chemical change is shown to be dictated by the quantum potential. The empirical parameters used in computer simulations such as molecular mechanics and dynamics are shown to derive in a fundamental way from the relationship between covalence and the golden ratio. 

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