UD researchers gain new insights into the hepatitis B virus genetic blueprint

Reviewed by Emily Henderson, B.Sc.August 13, 2020

Researchers at the University of Delaware are using supercomputing resources to work with scientists at the University of Indiana to update the virus that causes hepatitis B and the “pointed ball” that contains the genetic blueprint for the virus. I got a good understanding.

A study published online by the ACS Chemical Biology journal, ACS Chemical Biology, provides insight into what a capsid looks like. Assembles itself-a protein shell that protects the blueprint and facilitates its delivery to infect host cells.

Computer simulations conducted by UD scientists investigated the effects of mutations that impair the assembly process. The researchers, along with their co-workers, revealed that spikes, regions of the protein containing mutations, can communicate with regions of the protein that link other subunits to assemble the capsid. They found evidence that the shape change of the capsid protein switched it to the “on” state for assembly.

Scientists believe that capsid is an important target for developing drugs to treat hepatitis B, a life-threatening infectious disease that affects more than 250 million people worldwide. I will.

The capsid looks like a sharp ball, with 120 protein dimers assembled to form it. Each dimer contains spikes. Capsids are key to the viral infection cycle. If we could interfere with the assembly process, the virus would be unable to produce an infectious copy of itself. “

Jodi A. Hadden-Perilla, Associate Professor of Chemistry and Chemistry at UD, co-author of a new paper

Indiana University researchers study dimers, a bipartite T-shaped molecular structure, to investigate whether mutations activate or deactivate switches and turn on capsid assembly mechanisms. was doing. Together with the group of Hadden Perilla, they performed computer simulations to explain how mutation-induced changes in protein structure affected the ability of capsids to assemble.

“What we learned is that this mutation destroys the structure of the spikes on the top of the dimer,” said Hadden Perilla. “This mutation actually slows down assembly involving regions of the protein that are far away from the spike. It is clear that these two regions are connected. In particular, changes in protein shape at the spike. Please actually activate or deactivate the assembly.”

Her team performed what is known as all-atom molecular dynamics simulations using the Blue Waters Supercomputer, supported by the National Science Foundation at the University of Illinois Urbana Champaign.

Molecular dynamics simulations allow researchers to learn how molecules move and perform functions in nature. Computer simulation is the only way to reveal the movement of a molecular system down to the atomic level, and is sometimes called a “computational microscope”.

A paper titled “The integrity of the interdimer interface of the hepatitis B virus capsid protein dimer regulates capsid self-assembly” is available on the journal website.

Colombia to UD

For co-author of the thesis, PhD Carolina Perez Segura, manipulating the data from supercomputer simulation was a type of research experience that prompted her to take her to the University of Delaware and then stay.

“She made some important discoveries,” she said, exploring the effects of mutations through a large number of simulations and vast amounts of data, said Hadden Perilla. “I threw her deep into my new research group. [last summer], And she did a great job. “

Perez Segura came to UD as a participant in the University’s Latin American Summer Study Program. After graduating from the National University of Colombia (Columbia National University), this program marked the first time I left Colombia and made my first flight. She planned to study for a few months under Haden Perilla’s mentorship and then plan to return home.

But for her, the experience was so significant that she continued to work as a visiting researcher at Hadden Perilla while taking home plane tickets and applying to the UD PhD program. She was accepted and began studying during the spring semester.

She said it was her fascination with computational chemistry that took her to Delaware, and it was her job with a supercomputer that decided to continue the study.

“I was an undergraduate, but I chose that branch of chemistry as the type of career I wanted,” said Perez Segura, who worked for a small field research group in Colombia. “When I was introduced to the idea that mathematics and physics would help us understand biological processes, I knew that was what I wanted to do.

“I found it really great to be able to explain biological processes with numbers and computers. I wanted to learn more, but I have many opportunities here to learn.”

Although the social and travel restrictions imposed by the Coronavirus (COVID-19) pandemic have limited her ability to fully experience American life and culture, her experience at UD is still extremely high. Is positive to. She is more eager to go out and practice English and feel a part of American culture, while she is busy with exciting research, she said.

She is also currently working on studies that Hadden-Perilla is going to the virus that causes COVID-19.

“It’s rare for a student to be accepted into a graduate “off-cycle” program that begins in the spring semester,” said Hadden Perilla. “But Carolina is extraordinary.”