Dynamics of Protein Hydrophobic Cores by Deuteron Solid-State NMR Spectroscopy
|Funding Source||Research Corporation for Science Advancement|
|Last Updated||2010-09-24 16:40:52|
|Keywords||proteins, biophysics, computations|
In the past decade it became clear that the shapes/structures of proteins are not static – these molecules “breathe” and their structures fluctuate. It turned out that this breathing has important consequences for specific functions of proteins. The proposed project concentrates on the investigation of the motions (i.e., “breathing”) of a small model protein in its core region over a very broad range of conditions. The result will shed light on specifics of the motions and their importance in the biological functioning of the protein. To accomplish this goal, I will use experimental, theoretical, and computational approaches.
Hydrophobic cores are found in the interior of globular proteins and are essential for the formation of the folded state. They represent complex, dynamical media reflecting the existence of a conformational ensemble, which is important for various biological functions. Our goal is to investigate dynamical features typical in hydrophobic cores by looking at model globular proteins. We will employ deuteron NMR spectroscopy, which is ideally suited for investigation of dynamics over a wide range of time scales.
Our main system will be chicken villin headpiece subdomain, which represents one of the smallest examples of a cooperatively folding protein. Its small size makes it possible to use commercial solid-state peptide synthesis for sample preparation. We can thus easily obtain several samples with mutations in the core region and deuteron labels at chosen critical locations. Deuteron solid-state NMR measurements of quadrupolar echo line shapes and Zeeman and Quadrupolar order relaxation times will be conducted over 5K to 298K temperature range and then coupled to computational approaches to develop motional models for a detailed description of dynamics in the core region.
The results will likely advance our understanding of complex dynamical behavior of globular proteins.
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