Protein folding and viral infection

Understanding protein folding has many possible areas of biological and biomedical impact.  For example, consider one of the major research areas of the Kasson lab at the University of Virginia, namely how the influenza virus infects cells.  In the past, Dr. Kasson and Dr. Pande have studied two aspects of this:  how the influenza virus recognizes cell-surface receptors so it infects the "right" cell types and how small vesicles fuse.  

Dr. Kasson's group is now looking at the function of the viral protein that controls cell entry, a protein called hemagglutinin.  The hemagglutinin protein interacts with cell membranes:  one piece inserts into the membrane, refolds, and alters the membrane in some unknown manner to promote viral entry.  Another piece links the viral and cell membranes and refolds to bring the two together.  We are running simulations on Folding@Home to examine each of these pieces.  Dr. Kasson's laboratory also looks at these processes experimentally.   

Both of these problems involve protein folding.  This extends the problem of understanding folding beyond the "canonical" model of an unstructured protein in water taking on a final shape but instead in the first case a small protein inserting into a lipid membrane and changing shape in response to its environment and in the second case a large protein changing from one shape to another in response to physiological cues.  One could consider these special cases of protein folding or how viruses use protein folding to infect cells. 

Future posts will address methods we have developed to assist in these studies as well as other important problems we work on.  We are also doing methodological work that will improve the efficiency of running Folding@Home simulations and analyzing the results.  The Folding@home community has made an important contribution in providing the computing power for these studies (you can see some of our published work on the FAH papers page), and we are grateful to all involved.