Upload new images. The image library for this site will open in a new window.
Upload new documents. The document library for this site will open in a new window.
Show web part zones on the page. Web parts can be added to display dynamic content such as calendars or photo galleries.
Choose between different arrangements of page sections. Page layouts can be changed even after content has been added.
Move this whole section down, swapping places with the section below it.
Check for and fix problems in the body text. Text pasted in from other sources may contain malformed HTML which the code cleaner will remove.
Accordion feature turned off, click to turn on.
Accordion featurd turned on, click to turn off.
Change the way the image is cropped for this page layout.
Cycle through size options for this image or video.
Align the media panel to the right/left in this section.
Open the image pane in this body section. Click in the image pane to select an image from the image library.
Open the video pane in this body section. Click in the video pane to embed a video. Click ? for step-by-step instructions.
Remove the image from the media panel. This does not delete the image from the library.
Remove the video from the media panel.
These images show essential components of new HIV research
including (left to right): A mature HIV particle with perforations made
in a new technique developed by the University of Oxford; a new
atomistic computer model made by the lab of the University of Delaware’s
Juan Perilla; and the distinct ways metabolites bind to the capsid’s
structural elements — the six-sided hexamers (top right) and the
five-sided pentamers (bottom right).
Delaware researcher Juan Perilla is a computational scientist with the
heart of a storyteller. But he doesn’t want to tell computer stories. He
wants to tell stories about the life cycle of viruses.
Perilla has been studying the inner workings of viruses for years,
including the structure of the human immunodeficiency virus (HIV) and
how it exploits a protein found in human cells to sneak past immune
Now he has a new chapter to add. In a collaboration with Peijun
Zhang, professor of structural biology at the University of Oxford,
Perilla and two of his students have developed a computer model of the
HIV shell — known as a capsid — that shows the whole 77-million atom
system, how it moves and interacts with other cells.
Understanding this structure and especially its interactions with
other cells could lead to new medicines to fight the virus that causes
AIDS (acquired immunodeficiency syndrome). That would be good news for
the estimated 38 million people living with HIV around the world.
A paper describing this work was published Friday, Nov. 19, in the journal Science Advances.
Perilla, assistant professor of chemistry and biochemistry at UD, and
Zhang have known each other for at least 10 years, he said. This
collaboration drew on the expertise of both of their labs.
Zhang and her team at Oxford used a new approach and state-of-the-art
technology to show that perforating the membrane of an HIV particle
allowed proteins and small molecules to reach its capsid, where the
virus’s genome is stored. They then investigated how the capsid
interacted with two specific molecules — one called CypA (cyclophilin
A), the other IP6 (inositol hexakisphosphate). Those interactions are
essential to the spread of the virus.
Perilla and his team used the data from the Oxford lab and supercomputers to build their model.
“This has atomistic precision,” Perilla said. “The ions, the cations,
all of the hydrogens — it’s an atomistic view of the process, not an
approximation. It’s as accurate as it gets. And we are able to tell the
story from a biological point of view.”
Move this whole section up, swapping places with the section above it.
A new high-precision model of the HIV capsid has been developed by
Juan Perilla, assistant professor of chemistry and biochemistry at the
University of Delaware (left) and recently graduated students Tanya
Nesterova (center) and Chaoyi Xu.
“Free-energy” calculations are key to the model. These take all kinds
of molecular dynamics into consideration, including potential of mean
force (PMF), which is something like buoyancy or magnetism, sometimes
drawing particles in, sometimes pushing them away. These dynamics are
critical to the value of any model.
Some calculations were developed by Tanya Nesterova, an undergraduate
student who had a double major in chemistry and applied mathematics.
She has since graduated from UD and is now in a doctoral program at
Johns Hopkins University. Also key to this work was Chaoyi Xu, a
doctoral student in Perilla’s lab who has successfully defended his
dissertation and now works as a computational chemist in the
“The combination of theory and experiments gives us an opportunity to
train these very talented students,” Perilla said. “And this requires a
very special kind of student — someone who studies physics, computing
and math and wants to do something as far-fetched as biology. It’s hard
to cross that barrier. I’ve been extremely privileged to work with these
The model shows important targets that drug developers could explore, Perilla said.
“This is essential,” he said. “Millions of years of evolution have driven the virus in this direction.”
And this model could provide an important path forward for addressing other viruses, Zhang said.
“In collaboration with Prof. Juan Perilla’s group at the University
of Delaware, using information derived from electron tomography, we also
built an atomistic model of the whole HIV capsid which could serve as a
blueprint for the development of capsid-targeting antivirals,” she
said. “The perforation on the enveloped virus membrane also provides a
novel approach to study host-virus interactions for other viral
Perilla and his lab have extensive experience in virus studies, including HIV, COVID-19, hepatitis B, and Ebola.
“I’m looking forward to seeing how my students develop,” Perilla
said. “They’re the future. They’ve been through a pandemic and been
trained through HIV. They are the ones who are going to tackle the
problems when I’m old and I have no doubt they’ll succeed.”
Many questions remain about what these molecules and metabolites are doing, but this work adds to the narrative.
“Even though HIV is one of the most studied viruses, there are so
many questions that remain unclear or under debate about how HIV infects
and replicates in the cell,” said Xu. “By investigating HIV in detail,
it not only gives us new knowledge about fighting the ongoing HIV/AIDS
epidemic, but also insights about the replication cycles of other
The collaboration was an amazing experience, Xu said.
“We are very happy to see that our collaboration made some impacts
that we would not achieve individually,” he said. “I personally also
learned a lot by working with the researchers and students from other
labs and different backgrounds.”
Perilla hopes many more students will be drawn to this work.
“The U.S. has extremely strong, well-trained people who can produce
pharmaceuticals,” Perilla said. “But a very thin part of the population
devotes their lives to this work. We need more opportunities to bring
people to science and have them be successful in science. The talent is
out there. We just need more people.”
In addition to Zhang, this collaborative work included scientists
from the Electron Bio-Imaging Centre (eBIC), which she directs, and
partners at the University of Pittsburgh School of Medicine, the School
of Medical Sciences in Sydney, Australia, the University of Melbourne
and St. Vincent’s Institute of Medical Research in Victoria, Australia.
The lead authors of the Science Advances article were Tao Ni and Yanan
Zhu of the University of Oxford.
Support for the work came from multiple sources, including the
National Institutes of Health, the Wellcome Trust, the United Kingdom’s
Biotechnology and Biological Sciences Research Council and the
Australian Research Council.
Juan Perilla is an assistant professor in the Department of Chemistry and Biochemistry
at the University of Delaware. He earned his doctorate at Johns Hopkins
University and did postdoctoral work at the University of Illinois at
Urbana-Champaign before joining the UD faculty.
Article by Beth Miller;
Photo illustration by Jeffrey C. Chase; Photos by Kathy F. Atkinson and courtesy of Juan Perilla and Diamond Light Source
Published November 19, 2021