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Re-Wiring Protein Structures

Philippa J. Reeder, Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 8th St, Troy, NY 12180, Jonathan Dordick, Chemical & Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, and Christopher Bystroff, Biology, Rensselaer Polytechnic Institute, 110 8th St, Troy, NY 12180.

This work focuses on design and improvement of functional protein properties, primarily protein stability, by a novel method: protein structure re-wiring. A structure-based protein redesign method, it is focused on direct improvement of protein kinetic stability with minimal effect on protein activity. We hypothesize in this work that enzyme function is primarily conferred by intramolecular contacts between secondary structural units. By maintaining such interactions (and therefore the majority of residue-residue contacts) and intelligently changing the way in which those structural units are connected (i.e., re-wiring it), we demonstrate that it is possible to change the rate of unfolding of a model protein, GFP, without effecting its activity. This method may be universal and therefore applied to any protein with multiple structural units.


Web Page: www.rpi.edu/~reedep/work.html