Determining Structural Ensembles for Intrinsically Unstructured Proteins Grant uri icon

Overview

abstract

  • The objective of this project to is study structural variations in a family of intrinsically unstructured proteins (IUP). Based on the PI's previous work, and the work of others, it is now clear that IUPs form a diverse set of protein families that can elicit biological function using a variety of mechanisms. This project has two aims: (I) Determine structural ensembles for a set of homologous proteins that are intrinsically unstructured. In this specific aim, paramagnetic relaxation enhancement will be used to estimate long-range interatomic distances that can be used to restrain structure calculations. The structural ensembles will then be validated using residual dipolar couplings and small angle x-ray scattering. (II) Determine the relationship between sequence identity and structural similarity for a set of homologous proteins that are intrinsically unstructured. In this specific aim, eigenvector decomposition of protein contact maps will be used to identify similarities between the structural ensembles. This data will then be correlated with genetic distance matrices to determine the percent sequence identity necessary for structural similarity. Experiments in this specific aim will also test the importance of amino acid composition for specifying the structural ensemble. Successful completion of both specific aims will facilitate the development of models of protein evolution for intrinsically unstructured proteins that can be used to estimate their dynamic structures based on sequence identity.

    The PI has a strong record of advancing discovery and understanding while promoting teaching, training, and learning. This is evidenced by the three peer reviewed publications that have undergraduate students as authors and five peer reviewed publications that have authors from underrepresented groups. The PI is also very committed in disseminating scientific information to general public. In the summer of 2004, the PI participated in a state funded workshop for secondary education to science teachers. The PI gave lectures on the general principles of protein structure and function as well as a tutorial for using molecular graphics programs in the classroom. This project will involve two undergraduate students and a female research technician and the PI will continue his efforts to involve science teachers in basic scientific research by holding an annual workshop whose purpose would be to introduce science teachers to the latest breakthroughs and make them aware of new web-based tools for scientific discovery.

date/time interval

  • April 15, 2008 - June 30, 2009

total award amount

  • 289,522

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