9513355 Zuiderweg Dr. Zuiderweg will develop new NMR spectroscopy methodologies for the study of dynamics in biological macromolecules by measuring 13 CO and 15ND relaxation in 13C/15N labeled proteins. These experiments will yield information on the dynamics of the protein backbone and nitrogen-containing sidechains, complementary to the information obtained from the commonly performed 15NH NMR relaxation experiments. Efforts will go into extending above methods to allow the detection of the presence or absence of cross correlation between relaxation mechanisms. Such measurements will help the development of models for dynamical phenomena in proteins. The cross correlation (interference) between the heteronuclear relaxation mechanisms is determined with new two- and three-dimensional NMR methods. The methods will be mostly developed with the proteins T4-lysozyme (19 kDa) and Binase (12 kDa), and using a peptide loop on the protein Hsc70. Preliminary data shows that the extent of relaxation cross correlation is non-uniform over the backbone of T4-lysozyme, indicating that the dynamical characteristics measured as such are non-uniform and therefore of high informational content. The methods will be extended for determining the extent of motional correlation between relaxation vectors in protein surface loops, using the Hsc70 protein. These methods will be well-suited to distinguish between disjointed-chain motions and concerted motions involving only a few hinge-points. This information should be of importance for the understanding of the role of those loops and peptides that are involved in intermolecular interactions. %%% The research is aimed at developing new nuclear magnetic resonance (NMR) spectroscopy methodologies for the study of dynamics in biological macromolecules. The methods will concentrate on the NMR relaxation behavior of carbonyl moieties and will yield information on the dynamics of the protein backbone, complementary to the information obtained from the commonly performed NMR relaxation experiments focusing on amide moieties. The methods will be mostly developed with the proteins T4-lysozyme and Binase and will be extended for determining the extent of motional correlation between relaxation vectors in protein surface loops. This information should be of importance for the understanding of the dynamical characteristics of loops and peptides that are involved in intermolecular interactions. ***
