Poster abstracts

Poster number 11 submitted by Brandon Sullivan

Statistical approaches to elucidate the determinants of protein stability

Brandon J. Sullivan (The Ohio State Biochemistry Program, The Ohio State University), Venuka Durani (Department of Chemistry, The Ohio State University), Tran Nguyen (Department of Molecular Genetics, The Ohio State University), Thomas J. Magliery (Department of Chemistry and Biochemistry, The Ohio State University)

Abstract:
The marginal stability of natural proteins presents challenges in understanding diseases as well as production and administration of protein drugs. Currently, there are no reliable methods to predict the thermodynamic consequence of even a single mutation. In the post-genomic era the application of sequence statistics is an attractive candidate for designing proteins and further understanding the sequence-structure relationship. Our lab has developed and empirically validated the roles of conservation and statistical correlation in the triosephosphate isomerase family. First, we established several statistical parameters that accurately select which consensus mutations will improve the thermostability of a wild-type TIM. Second, we designed and characterized two consensus TIMs that differ dramatically in their enzymatic activity and biophysical properties, despite differing at only a small number of highly variable positions. Third, we have developed new methodologies for observing statistical correlations within protein families and have characterized their effects in TIM.

Keywords: Bioinformatics, TIM-barrel, Protein Stability