The results of the study, published in the journal Structure, show how this particular protein changes shape as the virus infects a cell and identify possible targets for potential therapies.
“The nucleocapsid protein of the Ebola virus plays an important role in the virus replication process,” says study lead Rumela Chakrabarti, a bioengineer and associate adjunct professor at the UC San Diego Jacobs School of Engineering and Skaggs School of Pharmacy and Pharmaceutical Sciences. “This protein encapsidates the virus’ genetic material. It’s like bubble-wrap for the virus RNA, protecting it from damage and from the cell’s immune response. The more we understand about the structure of this protein and how it functions, the better chance we have of finding new ways to treat the virus.”
Chakrabarti and her team chose to investigate the Ebola nucleocapsid protein using specialized simulations called “enhanced sampling” molecular dynamics. This computational approach allows scientists to simulate the movements of individual atoms in the protein, revealing how the protein changes over time and exposing weak points in the protein structure.
The team ran these extensive computer simulations on Stampede2. The researchers say they needed the power and scalability of Stampede2 in order to run thousands of simulations, each of which took several days.
“The Stampede2 system allowed us to simulate large conformational changes of the protein structure, which provides insights into how it might behave inside an infected cell,” says Chakrabarti.
The simulations revealed several possible targets for potential new therapies, including the flexible regions of the protein that change the most during infection. These areas could be targeted by small molecules or antibodies, preventing them from performing their function and ultimately protecting the host cell from infection.
“Our next steps will be to design specific drugs or drug-like molecules that can bind to these pockets in order to reduce viral replication and infectivity,” says Chakrabarti.
This research was supported in part by the National Institutes of Health and the Department of Defense. Computations were performed on the Stampede2 system at the TACC.
