DESIGN OF RECEPTOR BINDERS
The overall focus of the project is to build proteins that will interact with receptors on the epithelial cells which are the main building blocks of the blood–brain barrier (BBB). These proteins will be used to determine the possible molecular mechanism of BBB crossing with the long-term goal to couple various therapeutics to the designed carriers for improved treatment of nervous system diseases. Specifically we are working with the transferrin receptor which has been demonstrated to bind and likely shuffle transferrin as well as different antibodies across the BBB. To our help we are using Rosetta, a state-of-the-art computational protein engineering software, to construct proteins that will interact with our target; these are then characterized experimentally by standard biochemical and molecular biology techniques in the lab.
EVALUATION OF PROTEIN–PROTEIN BINDING ENERGIES IN COILED COILS
Dimeric coiled coils are the simplest form of a protein–protein interface with two alpha helices supercoiling around each other. While their overall structure can be described by simple parametric equations, the binding energy between the two monomers cannot be assessed reliably by the existing methods. We investigate by computational modeling the guiding principles of monomer association in coiled coil formation and evaluate the relative binding energies between different pairings of coiled coils to determine the preferences of oligomerization. Finally we correlate our calculated date with the experimental determined values so that we can build better predictive models for evaluation of designed protein interactions.