"We have all the details down to
the atomic level,” she said. “You need that to develop a complete
understanding of the molecule and to study drug interactions.”
The researchers also found that small triangular openings, or pores,
in the capsid surface are likely the location where its protein “tails”
poke through, sending a signal that is essential to the infection
“We know that the capsid tails have to be exposed to the surface at
some time for the capsid to travel to the cell nucleus,” Hadden said.
“It’s like hailing a taxi.”
All the findings have the potential to lead to drug treatments, she
said. For example, if the capsid could be made rigid and unable to
distort or if a way could be found to block the triangular pores in its
surface, the infection process might be halted.
There’s an effective vaccine to prevent hepatitis B, but no cure once
a person is infected. The virus causes severe liver disease, which can
lead to potentially fatal conditions such as cirrhosis and liver cancer.
More about the research
The paper is available online at eLife, a peer-reviewed, open-access scientific journal for the biomedical and life sciences.
Co-authors, with Hadden and Perilla, are Christopher John Schlicksup,
Balasubramanian Venkatakrishnan and Adam Zlotnick, all of Indiana
University, and the late Klaus Schulten of the University of Illinois at
Urbana-Champaign (UIUC), who pioneered the application of all-atom
molecular dynamic simulations to study complete virus capsids.
The research was supported by UD, through a postdoctoral fellowship
to Hadden, and the National Institutes of Health, through a Center of
Biomedical Research Excellence Grant to Perilla and a Biomedical
Technology Research Resource to Schulten. The computer simulations were
made possible by the Blue Waters project, a joint effort of UIUC and its
National Center for Supercomputing Applications.
Article by Ann Manser; photo by Kathy F. Atkinson; photo illustration by Jeffrey Chase