The functions of proteins, nucleic acids and polysaccharides are intimately connected to their covalent structures, their conformations, and the proximity of solvent and other solute molecules. Knowledge of the structures of these molecules in solution is an essential part of understanding their function in living organisms and is necessary for the rational design of drugs. Nuclear magnetic resonance spectroscopy has emerged as the most powerful method for determining structures of these molecules in solution. However, as such molecules become larger, nmr methods for structural studies begin to falter and the use of elaborate pulse sequences, often in concert with placement of isotopes of carbon, nitrogen or deuterium in the molecule of interest, becomes necessary to obtain the needed experimental information. Such experiments can produce unexpected results and in these cases it is only by recognizing the underlying theory that reliable interpretations of results be made. The best procedure to validate conclusions in these cases is to simulate the experiment using a mathematical treatment that takes into account rigorously all relevant aspects of the experiment. This proposal seeks support for continuation of efforts to develop methods for the simulation of nmr experiments by a computer program that includes, in general a way, the effects of nuclear spin relaxation, r.f. fields, and chemical exchange. Such simulations could be used directly in the interpretation of experimental results or could be used to test more approximate theoretical methods so that the accuracy of interpretations of experimental data based on the approximate treatments can be assessed. The project will include extensive comparisons with theoretical and experimental work in the literature, carried out in collaboration with workers at other institutions, or in this laboratory. The project is based on appreciable preliminary work and is timely because many of the effects detected that could lead to errors of interpretation become important at the higher magnetic fields that are now becoming available.
| Cuperlovic, M; Meresi, G H; Palke, W E et al. (2000) Spin relaxation and chemical exchange in NMR simulations. J Magn Reson 142:23-Nov |
| Meresi, G H; Cuperlovic, M; Palke, W E et al. (1999) Pulsed field gradients in simulations of one- and two-dimensional NMR spectra. J Magn Reson 137:186-95 |
