Protein Design
The ultimate goal of protein design is to take a set of functional specifications for a theoretical protein and then generate an actual protein that exhibits the desired functions. For example, given a binding target, the ideal protein design algorithm should be able to predict a protein sequence that can specifically bind the provided target. Thus, the applications of these algorithms to both medical therapeutics and basic cellular research are limited only by a researcher's creativeness (and available structural information). While the protein design field has not yet matured to this point, there have been several advances including introduction of novel enzymatic activity into a protein as well as switching a protein's binding specificity.I work on developing new design algorithms that accurately model protein flexibility while guaranteeing the optimal protein design is found given the input model. I specifically focus on designing protein-protein interactions (PPIs). PPIs are ubiquitous in nature and play important roles in both causing disease and disease prevention, which makes them a prime target for protein design.
Designing CAL Inhibitors
Cystic fibrosis (CF) is an inherited disease that causes the body
to produce thick mucus that clogs the lungs and obstructs the
breakdown and absorption of food. The cystic fibrosis transmembrane
conductance regulator (CFTR) is mutated in CF patients, and the
most common mutation causes three defects in CFTR: misfolding,
decreased function, and rapid degradation. Drugs are currently
being studied to correct the first two CFTR defects, but the
problem of rapid degradation remains. Recently, key protein-protein
interactions have been discovered that implicate the protein CAL in
CFTR degradation. I am using our protein design algorithms to develop
peptide inhibitors of the CAL-CFTR interface.