Nuclear magnetic resonance structural modeling

Besides the classical techniques for structural determination of proteins, namely X-ray diffraction or nuclear magnetic resonance, molecular modelling has become a complementary approach, providing refined structural details [4—7]. This view on the atomic scale paves the way to a comprehensive smdy of the correlations between protein structure and function, but a realistic description relies strongly on the performance of the theoretical tools. Nowadays, a full size protein is treated by force fields models [7-10], and smaller motifs, such as an active site of an enzyme, by multiscale approaches involving both quantum chemistry methods for local description, and molecular mechanics for its environment [11]. However, none of these methods are ab initio force fields require a parameterisation based on experimental data of model systems DPT quantum methods need to be assessed by comparison against high level ab initio calculations on small systems. 

Chen, J., Dupradeau, R Y., Case, D. A., Turner, C. J., Stubbe, J. (2007). Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4 -oxidized abasic sites. Biochemistry, 46, 3096. 

Nuclear magnetic resonance (NMR) spectroscopy is a valuable technique for obtaining chemical information. This is because the spectra are very sensitive to changes in the molecular structure. This same sensitivity makes NMR a difficult case for molecular modeling. 

FIG. 23 Comparison of various one-parameter diffusion models. (Reproduced with permission from Ref. 448, Analysis of Diffusion and Structure in Polyacrylamide Gels by Nuclear Magnetic Resonance, M.S. Thesis, Florida State University, Copyright 1997, Brigita Penke.)... 

Flohr S, Kurz M, Kostenis E, Brkovich A, Fournier A, Klabunde T. Identification of nonpeptidic urotensin II receptor antagonists by virtual screening based on a pharmacophore model derived from structure-activity relationships and nuclear magnetic resonance studies on urotensin II. J Med Ghent 2002 45 1799-805. 

To illustrate the utility of the MWBD method, a series of commercial polyvinyl acetates and low density polyethylenes are analyzed. Either kinetic models or 13c nuclear magnetic resonance results are used to estimate the branching structural parameter. 

F. Volke, A. Pampel 1995, (Membrane hydration and structure on a subnanometer scale as seen by high resolution solid state nuclear magnetic resonance POPC and P0PC/C12E04 model membranes), Biophys.J. 68, 1960-1965. 

Structural information at the molecular level can be extracted using a number of experimental techniques which include, but are not restricted to, optical rotation, infra-red and ultra-violet spectroscopy, nuclear magnetic resonance in the solid state and in solution, diffraction using electrons, neutrons or x-rays. Not all of them, however, are capable of yielding structural details to the same desirable extent. By far, experience shows that x-ray fiber diffraction (2), in conjunction with computer model building, is the most powerful tool which enables to establish the spatial arrangement of atoms in polymer molecules. 

The C-NMR spectrum ofindinavir sulfate, shown in Figure 13, was obtained using a Bruker Instruments model AMX-400 nuclear magnetic resonance spectrometer operating at a frequency of 100.55 MHz as an approximate 4.16 % w/v solution in deuterium oxide. The 67.4 ppm resonance of dioxane was used as an external reference standard. Peak assignments are found in Table 8, and make use of the numbered structural formula given previously [11]. 

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