Computational and experimental studies of integral membrane proteins folding and structure
We are interested in understanding the folding and structural properties of integral membrane proteins, and how these ultimately relate to their function.
Membrane proteins fold in a hydrophobic environment, following rules that are different than those that apply to soluble proteins. These rules, however, are still less understood because of the difficulties encountered when the traditional biophysical techniques are applied to membrane proteins.
To obtain much need structural and biophysical information, our laboratory adopts a multidisciplinary approach, using an integration of bioinformatics and experiments to reach beyond the limits of individual techniques.
We develop computational methods for high-throughput modeling and for the design of membrane proteins, as well as for the analysis of the database of high-resolution structures and genomic sequences. The computational side of our lab generates models and hypothesis that are tested in the "wet lab". In turn, the experimental outcome can feed back into further cycles of computation.
This approach allows us to ask general questions about the structural properties of membrane proteins (What are the rules that govern membrane protein folding? How is recognition achieved in the membrane? Can we predict membrane proteins structure and interaction partners from primary sequence alone?). We can also apply it to increase our functional understanding of specific biological systems (What is the stoichiometry of a complex? What amino acids are involved at the binding interface, and how will function be affected if we design a specific inhibitor against it?).
We use an integration of biophysical methods, molecular modeling,
sequence analysis, in vivo mutagenesis to obtain detailed structural model
of transmembrane proteins, and understand their folding, association and function.