We are interested in understanding the structural and dynamic information encoded in the linear amino acid sequence of proteins. The amino acid sequence not only contains the blueprint for the protein’s structure, but also encodes the various conformations available to the peptide chain; these conformational changes are relevant for folding, binding, and activity. Our lab uses a combination of biophysical, structural, biochemical, and computational techniques to translate sequence information into functional insights. 

Folding Through the Energy Landscape

We can describe the conformational space of a protein as an energy landscape. The amino acid sequence encodes not only the native state structure, but all the features of this landscape. We are interested in understanding the sequence-landscape relationship and extracting biophysical parameters from the sequence. 

Single Molecule Force Spectroscopy

Force spectroscopy with optical tweezers is a valuable technique that gives insight into the protein folding process at a single-molecule level. This technique can be used to understand the effect of mechanical force on the energy landscape of protein folding and unfolding, and to detect rare pathways and intermediates.

Two beads are attached to a molecule. One bead is tethered to a micropipette, the other to a laser trap, and force is applied. This technique can provide information on kinetics and thermodynamics of conformational changes measured by extension changes. 


In addition, we can study the role of osmolytes that can influence the energy landscape of a protein, and study it in the optical tweezer at the single-molecule scale. This gives us an additional "dimension" to our analysis, and provides more information regarding the specific pathways that the protein folds and unfolds. 



Moving Towards Functional and In Vivo Studies

Ultimately, biological processes take place in cells, and the cellular environment is often vastly different from the in vitro conditions. Factors such as crowding and the presence of other macromolecules play a role on protein folding and dynamics. In addition, protein synthesis off the ribosome takes place vectorally, raising additional questions regarding the structure and dynamics of the nascent polypeptide as it emerges from the ribosome. We are moving our studies into more cellular environments and tackling the question on co-translational folding. We are also exploring how protein dynamics play a role in signal transduction pathways.