Time scales for critical processes in biochemistry may range from many seconds or longer to small fractions of a psec depending on the nature of the critical process. Proteins and other macromolecules represent a small system which is sufficiently complex that motions and rearrangements may occur over a very wide range of frequencies or time scales. Many of these rearrangements may be critical for the function of the molecule or molecular assembly as a catalyst or other affector of chemical function in living material. Our knowledge of these time scales is often crude and approximate, and is often based on indirect measurements or deductions. Nuclear magnetic resonance and the associated relaxation spectroscopies provide a very direct and useful means for characterizing both intramolecular and intermolecular motions. However, the development of new experimental approaches to both liquids and solids offers new opportunity for dynamical characterization of proteins. The thrust of the present proposal is to apply a variety of magnetic resonance methods to study the proteins and protein interactions that will directly and specifically probe the time scales for macromolecular events from times on the order of seconds to time on the order of psec. The work proposed specifically addresses the time scales for major intramolecular structural fluctuations in proteins, their size and frequencies, the time scales for ion-macromolecule assocation, and the time scales for localized motion in macromolecules such as proteins. These properties will be studied as a function of solvent and cosolute composition using a multinuclear and multifrequency approach. Both solids, semi-solids and liquids will be included and measurements from very low magnetic fields to very high fields will be made. In short, our goal is the acquisition of selected spectral densities for particular magnetic interactions as a function of frequency which characterize known and specific pieces of the protein interactions.
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