Laufer Center Seminar

Computational design of protein misfits

The PDB contains tens of thousands of high-resolution structures, the vast majority of which are single-domain, globular, water-soluble proteins. ‘Misfits’ such as fibrous or membrane proteins are notably underrepresented in the PDB due to experimental challenges in their structure determination. This presents an obstacle for structure prediction and molecular design tools applied to atypical proteins, as most methods rely heavily on prior structural knowledge. Yet many of these misfits play central roles in biological processes and their malfunction can lead to disease states. Our laboratory combines computational protein design, molecular simulations, and a variety of experimental approaches to study protein misfits – with the goals of learning their roles in biology and disease, improving the accuracy of structure prediction and design tools, and developing synthetic proteins for biomedical / biotechnological applications.