Peripheral membrane proteins
The membranes of a cell are hotspots of biological activity. In turn, many diseases proceed through action near or within cellular membranes. Peripheral membrane proteins bind reversibly to the membrane, either through covalent or non-covalent means. Technical and methodological limitations have hindered a full understanding of this class of protein. We are interested in structural biology and high resolution functional study of these proteins. This information is used to inform rational drug design efforts to block the disease causing action of these proteins. The ultimate goal of the Fuglestad Lab is to inhibit peripheral membrane proteins for chemical biology investigations and to develop drugs to treat disease such as cancer and cardiovascular disorders.
Protein interactions with membranes and lipids
Understanding the interactions between peripheral membrane proteins and lipids is of paramount importance in strategizing therapeutics. We use a number of models of biological membranes to probe the interactions between proteins and cellular membranes. Of particular expertise in the Fuglestad Lab is leveraging reverse micelles as membrane mimics, which has several advantages over other more commonly used membrane models. We employ a multitude of techniques to study protein/membrane interactions including protein nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics simulations, fluorescence, and small-angle scattering, among others.
Fragment screening and inhibitor design
Rational design of inhibitors uses information about the structure and function of the protein target of interest. Fragment based approaches have recently come to prominence in inhibitor design. This involves screening proteins for small inhibitor building blocks rather than larger drug-like molecules. Peripheral membrane proteins are particularly challenging proteins for inhibitor and drug development. We employ established fragment screening methods and develop new technologies to enable fragment-based drug design of peripheral and membrane embedded proteins. The information gained form these screens are used in highly collaborative efforts in inhibitor development for the ultimate goal of obtaining chemical biology tools and drug leads.