Modeling Deadly viruses

Photo of Coray Colina

As a post-doc at University of North Carolina, Coray Colina investigated a new way of understanding blood coagulation diseases based on the movement of proteins. Using molecular dynamics, she was able to show that a protein called Factor VIIa has to be in contact with another protein called Tissue Factor to stop VIIa’s motion long enough for the clotting cascade to begin. The work gave her insight into how the motion of proteins can affect the active sites on proteins and viruses that new drugs are designed to attack, sometimes making the drugs lose their effectiveness.

Now at Penn State, she is doing similar work with biochemist Craig Cameron to understand the relationship between movement and function in an enzyme called polymerase, which helps viruses replicate and mutate. The Cameron lab has recently developed a model poliovirus to study how interfering with the speed and accuracy of replication in a virus can cause it to weaken dramatically.

Finding new vaccines to combat deadly viruses such as SARS or West Nile, or viruses that could be used as biological weapons, such as Ebola or smallpox, requires the production of an attenuated virus, a process involving slow, random mutations. With his model virus, professor Cameron hopes to create a universal strategy to speed up vaccine discovery and virus attenuation.

To help in that development, Colina models the polymerase process within the virus to gather information that is not available experimentally. Using x-rays of the frozen crystal structure of the virus, she can simulate the large proteins as they move. To test the validity of her simulation, she compares it to similar but smaller proteins that can be seen in motion using nuclear magnetic resonance imaging. Pulling the two techniques together, Colina can extrapolate the movement of the large proteins.

Coray Colina is associate professor of Materials Science and Engineering and co-director of the Center for the Study of Polymeric Systems. Craig Cameron is Paul Berg Professor of Biochemistry and Molecular Biology.

This research brief was featured in the brochure Biomedical Materials.