Our studies aim to answer the following questions: How do
we predict the binding specificities and energies of
protein-protein interactions from three-dimensional
structures alone? How do we engineer therapeutic molecules
that specifically abrogate disease-mediating
protein-protein interactions? Can we map disease-specific
interactomes and utilize this information to design
therapeutics?
We are primarily focused on the biophysical analysis and
identification of protein-protein interactions, including
those which we perturb by mutagenesis techniques in order
to derive a fundamental understanding about the nature of
how proteins recognize each other specifically, as well as
protein complexes that play key roles in disease
pathogenesis. Our main experimental tools include:
(1) surface plasmon resonance (SPR, or
Biacore) and isothermal titration
calorimetry (ITC) analysis for the derivation of
the kinetic and thermodynamic parameters of molecular
interactions;
(2) X-ray crystallography to determine the
atomic structures of proteins and protein complexes;
(3) tandem mass spectrometry (LC-MS/MS)
for the identification of proteins and post-translational
modifications involved in biomedically-relevant cellular
signaling events.
BBRI houses state-of-the art instrumentation for all of our
analytical needs, as part of our Core Facilities.
For more details about current
projects in the lab, click on the following links:
Superantigens: molecular basis of disease and
development of novel therapeutics
Protein-Protein Interactions:
quantifying energetic
cooperativity and the contributions to binding from
disordered protein regions