Our seminar on Feb 21, 2014 will be by CSB's Chris Negron! Hope to see you there!

Title: Experimental Characterization of Computationally Designed Orthogonal Antiparallel Homodimeric Coiled Coils

Abstract:
The fabrication of protein-based molecular devices, with atomic precision, remains to be a significant challenge for modern molecular engineers. However, nature has successfully developed many protein-based molecular devices through the exploitation of highly modular units such as the coiled coil. Coiled coils can be found in the assembly of many large macromolecular structures, and complex protein-protein interaction networks. And coiled coils have already been demonstrated to be useful reagents for molecular engineering. As a result, we have sought out to de novo design three orthogonal antiparallel homodimeric coiled coils. There are very few characterized antiparallel homodimers, and none have been measured for cross-reactivity. As a first step in accomplishing this goal we have measured the ability of several models to predict known properties of coiled coils. The top-performing model was combined with the CLASSY method, a sequence-based multi-state design framework, in order to allow for the computational design of the orthogonal antiparallel homodimeric coiled coils. The solution-phase biophysical properties of these designs have been characterized with a battery of assays. These designs represent a significant expansion to the existing standard protein interaction toolbox for molecular engineers.