Conformational Analysis of Peptide Models by Liquid-Crystal NMR

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Professor James Weisshaar of the University of Wisconsin Madison is supported by the Experimental Physical Chemistry program to perform experimental and theoretical studies on peptides oriented in liquid crystals using Nuclear Magnetic Resonance. This proposal seeks to make detailed experimental NMR measurements on the structures adopted by small model peptides in solution to calibrate and sharpen the accuracy of molecular force fields. Di-, tri- and possibly tetra- peptides will be studied in liquid crystals, a means by which the problem of the rapid tumbling and averaging of molecules in solution can be overcome. In order to fully characterize the peptides in their conformational diversity, a large number of magnetic dipole couplings between nuclear spins will be measured. The signals will be fit to those predicted from ab initio theory for a superposition of possible stable structures, with iterations on the distribution of conformers and on the force fields. Successful fitting for small, flexible peptides would provide an important step towards cracking the multi-conformation problem in flexible regions of proteins. NMR and X-ray methods, the two major methods for solving protein structures, are limited in characterizing the flexible local conformations within proteins. Computational approaches can assist in obtaining these conformations, however, the calculations are only as good as the force fields used. This proposal seeks to provide experimental data aimed at improving the calculations. It is especially timely because of the increasing massive efforts to calculate protein structures and protein folding processes.