9420203 Mayo 13C- and 15N-dipolar auto-and cross-correlation spectral densities and NOEs will be determined to systematically investigate backbone and side-chain rotational dynamics in short linear peptides. 13C- multiplet relaxation in methylene and methyl groups will provide unique motional information. Side-chain motions then will be better understood in the absence of most steric hinderences, e.g., the "unfolded," solvent-exposed state. Penta-peptides like G-G-X- G-G will be studied to assist in separating relaxation effects due to correlated internal rotations and overall molecular tumbling. The temperature dependence of all relaxation parameters will be investigated in order to derive rational energy barriers. Measurements will be done in water and in organic solvent, e.g., DMSO. In water, the effect of pH and varying ionic strength will assist in understanding electrostatic contributions to internal rotations. Restricted and unrestricted rotational diffusion, rotational fluctuation within potential wells, jump models, inclusion of internal rotational correlations, etc., and "model free" approaches will be used to analyze relaxation data, and molecular dynamics simulations and F,Y,C bond rotation energy profiles will be calculated for insight into which bond rotations may contribute most to these relaxation phenomena. %%% Proteins are composed of backbone atoms arranged in a repetitious polymeric array and specific side-chain groups that are arranged in a specific sequence. This sequence-specific arrangement of the twenty common side-chains tells, for example, a protein how to fold and what function it will have. In this study, NMR spectroscopy and computer modeling will be used to investigate fundamental processes of how small parts of proteins move and behave in solution. This in turn will provide a better understanding of protein backbone and side-chain internal motions and the influence of their motions on each other. In addition, due to the very nature of correlated motions in proteins, this study will set the stage for a better understanding of protein folding, the so-called "second genetic code." ***
