Understanding protein stability and activity using physical chemistry and bioinformatics

Please join Yale Chemistry for a Biophysical Student-Invited Seminar with Prof. Doug Barrick, T.C. Jenkins Professor of Biophysics, Johns Hopkins University.

Summary: The abundance of protein sequence data has significantly accelerated research and discovery in the areas of protein structure, function, evolution, and design. These studies have taken advantage of simple sequence metrics such as conservation, pairwise covariance between residues, and higher order sequence features leveraged by deep learning tools such as AlphaFold. In our lab we use sequence information at various levels of complexity to study protein folding, stability, and function. In one approach, we have used simple consensus information to design “average proteins”. We find these proteins to be of high (sometimes exceptionally high) stabilities. Using consensus design to simplify repeat proteins, we have created tandem repeat proteins that can be analyzed with a one-dimensional Ising model to quantify folding cooperativity. Results will be presented for a variety of repeat proteins, and extended to arrays of natural repeats with sequence heterogeneity. Studies applying consensus design to globular (non-repeat proteins) will also be presented which show consensus design to be a general strategy for stabilizing proteins, but sometimes with decreased enzyme activity. We have recently begun to design proteins including pairwise covariance in addition to single-site conservation and have been surprised to find that stability is determined by single-site bias but not pairwise covariance, whereas enzyme activity seems to be promoted by covariance.

For more information on Prof. Barrick's research: Barrick Lab | Johns Hopkins University

This seminar is supported by the Biophysical Training Grant