PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

First complete coronavirus model shows cooperation

Frontera, Anton 2 supercomputers simulate holistic model of SARS-CoV-2 virion

2021-02-25
(Press-News.org) The COVID-19 virus holds some mysteries. Scientists remain in the dark on aspects of how it fuses and enters the host cell; how it assembles itself; and how it buds off the host cell.

Computational modeling combined with experimental data provides insights into these behaviors. But modeling over meaningful timescales of the pandemic-causing SARS-CoV-2 virus has so far been limited to just its pieces like the spike protein, a target for the current round of vaccines.

A new multiscale coarse-grained model of the complete SARS-CoV-2 virion, its core genetic material and virion shell, has been developed for the first time using supercomputers. The model offers scientists the potential for new ways to exploit the virus's vulnerabilities.

"We wanted to understand how SARS-CoV-2 works holistically as a whole particle," said Gregory Voth, the Haig P. Papazian Distinguished Service Professor at the University of Chicago. Voth is the corresponding author of the study that developed the first whole virus model, published November 2020 in the Biophysical Journal.

"We developed a bottom-up coarse-grained model," said Voth, "where we took information from atomistic-level molecular dynamics simulations and from experiments." He explained that a coarse-grained model resolves only groups of atoms, versus all-atom simulations, where every single atomic interaction is resolved. "If you do that well, which is always a challenge, you maintain the physics in the model."

The early results of the study show how the spike proteins on the surface of the virus move cooperatively.

"They don't move independently like a bunch of random, uncorrelated motions," Voth said. "They work together."

This cooperative motion of the spike proteins is informative of how the coronavirus explores and detects the ACE2 receptors of a potential host cell.

"The paper we published shows the beginnings of how the modes of motion in the spike proteins are correlated," Voth said. He added that the spikes are coupled to each other. When one protein moves another one also moves in response.

"The ultimate goal of the model would be, as a first step, to study the initial virion attractions and interactions with ACE2 receptors on cells and to understand the origins of that attraction and how those proteins work together to go on to the virus fusion process," Voth said.

Voth and his group have been developing coarse-grained modeling methods on viruses such as HIV and influenza for more than 20 years. They 'coarsen' the data to make it simpler and more computationally tractable, while staying true to the dynamics of the system.

"The benefit of the coarse-grained model is that it can be hundreds to thousands of times more computationally efficient than the all-atom model," Voth explained. The computational savings allowed the team to build a much larger model of the coronavirus than ever before, at longer time-scales than what has been done with all-atom models.

"What you're left with are the much slower, collective motions. The effects of the higher frequency, all-atom motions are folded into those interactions if you do it well. That's the idea of systematic coarse-graining."

The holistic model developed by Voth started with atomic models of the four main structural elements of the SARS-CoV-2 virion: the spike, membrane, nucleocapsid, and envelope proteins. These atomic models were then simulated and simplified to generate the complete course-grained model.

The all-atom molecular dynamics simulations of the spike protein component of the virion system, about 1.7 million atoms, were generated by study co-author Rommie Amaro, a professor of chemistry and biochemistry at the University of California, San Diego.

"Their model basically ingests our data, and it can learn from the data that we have at these more detailed scales and then go beyond where we went," Amaro said. "This method that Voth has developed will allow us and others to simulate over the longer time scales that are needed to actually simulate the virus infecting a cell."

Amaro elaborated on the behavior observed from the coarse-grained simulations of the spike proteins.

"What he saw very clearly was the beginning of the dissociation of the S1 subunit of the spike. The whole top part of the spike peels off during fusion," Amaro said.

One of the first steps of viral fusion with the host cell is this dissociation, where it binds to the ACE2 receptor of the host cell.

"The larger S1 opening movements that they saw with this coarse-grained model was something we hadn't seen yet in the all-atom molecular dynamics, and in fact it would be very difficult for us to see," Amaro said. "It's a critical part of the function of this protein and the infection process with the host cell. That was an interesting finding."

Voth and his team used the all-atom dynamical information on the open and closed states of the spike protein generated by the Amaro Lab on the Frontera supercomputer, as well as other data. The National Science Foundation (NSF)-funded Frontera system is operated by the Texas Advanced Computing Center (TACC) at The University of Texas at Austin.

"Frontera has shown how important it is for these studies of the virus, at multiple scales. It was critical at the atomic level to understand the underlying dynamics of the spike with all of its atoms. There's still a lot to learn there. But now this information can be used a second time to develop new methods that allow us to go out longer and farther, like the coarse-graining method," Amaro said.

"Frontera has been especially useful in providing the molecular dynamics data at the atomistic level for feeding into this model. It's very valuable," Voth said.

The Voth Group initially used the Midway2 computing cluster at the University of Chicago Research Computing Center to develop the coarse-grained model.

The membrane and envelope protein all-atom simulations were generated on the Anton 2 system. Operated by the Pittsburgh Supercomputing Center (PSC) with support from National Institutes of Health, Anton 2 is a special-purpose supercomputer for molecular dynamics simulations developed and provided without cost by D. E. Shaw Research.

"Frontera and Anton 2 provided the key molecular level input data into this model," Voth said.

"A really fantastic thing about Frontera and these types of methods is that we can give people much more accurate views of how these viruses are moving and carrying about their work," Amaro said.

"There are parts of the virus that are invisible even to experiment," she continued. "And through these types of methods that we use on Frontera, we can give scientists the first and important views into what these systems really look like with all of their complexity and how they're interacting with antibodies or drugs or with parts of the host cell."

The type of information that Frontera is giving researchers helps to understand the basic mechanisms of viral infection. It is also useful for the design of safer and better medicines to treat the disease and to prevent it, Amaro added.

Said Voth: "One thing that we're concerned about right now are the UK and the South African SARS-CoV-2 variants. Presumably, with a computational platform like we have developed here, we can rapidly assess those variances, which are changes of the amino acids. We can hopefully rather quickly understand the changes these mutations cause to the virus and then hopefully help in the design of new modified vaccines going forward."

INFORMATION:

The study, "A multiscale coarse-grained model of the SARS-CoV-2 virion," was published on November 27, 2020 in the Biophysical Journal. The study co-authors are Alvin Yu, Alexander J. Pak, Peng He, Viviana Monje-Galvan, Gregory A. Voth of the University of Chicago; and Lorenzo Casalino, Zied Gaieb, Abigail C. Dommer, and Rommie E. Amaro of the University of California, San Diego. Funding was provided by the NSF through NSF RAPID grant CHE-2029092, NSF RAPID MCB-2032054, the National Institute of General Medical Sciences of the National Institutes of Health through grant R01 GM063796, National Institutes of Health GM132826, and a UC San Diego Moore's Cancer Center 2020 SARS-COV-2 seed grant. Computational resources were provided by the Research Computing Center at the University of Chicago, Frontera at the Texas Advanced Computer Center funded by the NSF grant (OAC-1818253), and the Pittsburgh Super Computing Center (PSC) through the Anton 2 machine. Anton 2 computer time was allocated by the COVID-19 HPC Consortium and provided by the PSC through Grant R01GM116961 from the National Institutes of Health. The Anton 2 machine at PSC was generously made available by D. E. Shaw Research."



ELSE PRESS RELEASES FROM THIS DATE:

Imaging space debris in high resolution

Imaging space debris in high resolution
2021-02-25
Litter is not only a problem on Earth. According to NASA, there are currently millions of pieces of space junk in the range of altitudes from 200 to 2,000 kilometers above the Earth's surface, which is known as low Earth orbit (LEO). Most of the junk is comprised of objects created by humans, like pieces of old spacecraft or defunct satellites. This space debris can reach speeds of up to 18,000 miles per hour, posing a major danger to the 2,612 satellites that currently operate at LEO. Without effective tools for tracking space debris, parts of LEO may even become too hazardous for satellites. In a paper publishing today in the SIAM Journal on Imaging Sciences, Matan Leibovich (New York University), George Papanicolaou (Stanford University), and Chrysoula Tsogka (University of California, ...

Social dilemma follows 2018 eruption of Kilauea volcano

Social dilemma follows 2018 eruption of Kilauea volcano
2021-02-25
The unprecedented cost of the 2018 Kilauea eruption in Hawai'i reflects the intersection of distinct physical and social phenomena: infrequent, highly destructive eruptions, and atypically high population growth, according to a new study published in Nature Communications and led by University of Hawai'i at Mānoa researchers. It has long been recognized that areas in Puna, Hawai'i, are at high risk from lava flows. This ensured that land values were lower in Puna--which lies within the three highest risk lava hazard zones 1, 2 and 3--which actively promoted rapid population ...

Signal transduction without signal -- receptor clusters can direct cell movement

2021-02-25
Our body consists of 100 trillion cells that communicate with each other, receive signals from the outside world and react to them. A central role in this communication network is attributed to receiver proteins, called receptors, which are anchored at the cell membrane. There, they receive and transmit signals to the inside of the cell, where a cell reaction is triggered. In humans, G protein-coupled receptors (GPC receptors) represent the largest group of these receptor molecules, with around 700 different types. The research of the Frankfurt and Leipzig scientists focused on a GPC receptor that serves as a receptor for the ...

Urban Americans more likely to follow covid-19 prevention behaviors than rural Americans

2021-02-25
Timothy Callaghan, PhD, and Alva Ferdinand, DrPH, JD, from the Southwest Rural Health Research Center at Texas A&M University School of Public Health, joined colleagues in the first national study of how often people in urban and rural areas in the United States follow COVID-19 guidelines. These include public health best practices like wearing masks in public, sanitizing homes and work areas, maintaining physical distancing, working from home and avoiding dining in restaurants or bars. The research team used a survey of 5,009 U.S. adults that closely matched the makeup of the country's population as a whole. The survey asked how often participants followed COVID-19 prevention recommendations and collected data on political ideology, perceived risk ...

New sustainable building simulation method points to the future of design

2021-02-25
ITHACA, N.Y. - A team from Cornell University's Environmental Systems Lab, led by recent graduate Allison Bernett, has put forth a new framework for injecting as much information as possible into the pre-design and early design phases of a project, potentially saving architects and design teams time and money down the road. "(Our framework) allows designers to understand the full environmental impact of their building," said Bernett, corresponding author of "Sustainability Evaluation for Early Design (SEED) Framework for Energy Use, Embodied Carbon, Cost, and Daylighting Assessment" which published Jan. 10 in the Journal of ...

Scientists use Doppler to peer inside cells

Scientists use Doppler to peer inside cells
2021-02-25
WEST LAFAYETTE, Ind. -- Doppler radar improves lives by peeking inside air masses to predict the weather. A Purdue University team is using similar technology to look inside living cells, introducing a method to detect pathogens and treat infections in ways that scientists never have before. In a new study, the team used Doppler to sneak a peek inside cells and track their metabolic activity in real time, without having to wait for cultures to grow. Using this ability, the researchers can test microbes found in food, water, and other environments to see if they are pathogens, or help them identify the right medicine to treat antibiotic-resistant bacteria. David Nolte, Purdue's Edward ...

Farmers in developing countries can protect both profits and endangered species

2021-02-25
HOUSTON - (Feb. 25, 2021) - Low-income livestock farmers in developing countries are often faced with a difficult dilemma: protect their animals from endangered predators, or spare the threatened species at the expense of their livestock and livelihood. A new paper by Rice University economist Ted Loch-Temzelides examines such circumstances faced by farmers in Pakistan. "Conservation, risk aversion, and livestock insurance: The case of the snow leopard" outlines a plan under which farmers can protect themselves from crippling financial losses while ...

Scientists identify cells responsible for liver tissue maintenance and regeneration

Scientists identify cells responsible for liver tissue maintenance and regeneration
2021-02-25
While the amazing regenerative power of the liver has been known since ancient times, the cells responsible for maintaining and replenishing the liver have remained a mystery. Now, research from the Children's Medical Center Research Institute at UT Southwestern (CRI) has identified the cells responsible for liver maintenance and regeneration while also pinpointing where they reside in the liver. These findings, reported today in Science, could help scientists answer important questions about liver maintenance, liver damage (such as from fatty liver or alcoholic liver disease), and liver cancer. The liver performs vital functions, including chemical detoxification, blood protein production, bile excretion, and regulation of energy metabolism. Structurally, the liver ...

Did teenage 'tyrants' outcompete other dinosaurs?

Did teenage tyrants outcompete other dinosaurs?
2021-02-25
Paleo-ecologists from The University of New Mexico and at the University of Nebraska-Lincoln have demonstrated that the offspring of enormous carnivorous dinosaurs, such as Tyrannosaurus rex may have fundamentally re-shaped their communities by out-competing smaller rival species. The study, released this week in the journal Science, is the first to examine community-scale dinosaur diversity while treating juveniles as their own ecological entity. "Dinosaur communities were like shopping malls on a Saturday afternoon ? jam-packed with teenagers" explained Kat Schroeder, a graduate student in the UNM Department of Biology who led the study. "They made up a significant portion of the individuals in a species and would have had a very real impact ...

NTU scientists develop laser system that generates random numbers at ultrafast speeds

NTU scientists develop laser system that generates random numbers at ultrafast speeds
2021-02-25
An international team of scientists has developed a system that can generate random numbers over a hundred times faster than current technologies, paving the way towards faster, cheaper, and more secure data encryption in today's digitally connected world. The random generator system was jointly developed by researchers from Nanyang Technological University, Singapore (NTU Singapore), Yale University, and Trinity College Dublin, and made in NTU. Random numbers are used for a variety of purposes, such as generating data encryption keys and one-time ...

LAST 30 PRESS RELEASES:

Ancient isolation’s impact on modern ecology

Synaptic protein change during development offers clues on evolution and disease

How commercial rooftop solar power could bring affordable clean energy to low-income homes

Taking a closer look at pulmonary fibrosis genetics

Cats with MDR1 mutation at risk of severe reactions to popular medication

IOP Publishing and IPEM mandate reporting of sex and gender in research 

Dogs trained to detect trauma stress by smelling humans’ breath

Electronic device thermal management made simpler and slightly better!

Study: Dangerous surgical site infections can be reduced with simple prevention protocol

Genetic testing of patients with atrial fibrillation can alert clinicians to potential development of life-threatening conditions

Artificial Intelligence tool successfully predicts fatal heart rhythm

What progress has China made in agriculture green development over the past five years?

ALMA finds new molecular signposts in starburst galaxy

Open waste burning linked to air pollution in Northwestern Greenland

Google Street View reveals how built environment correlates with risk of cardiovascular disease

Connecting the dots to shape growth forces

Parental avoidance of toxic exposures could help prevent autism, ADHD in children, new study shows

Trends in the incidence of renal replacement therapy due to rapidly progressive glomerulonephritis in Japan, 2006–2021

Olympics not likely to swallow up skateboarding’s subversive nature into its corporate spectacle, study says

Looking after the NHS workforce must be a top priority, say experts

Prolonged use of certain hormone drugs linked to increased brain tumor risk

Delirium a ‘strong risk factor’ for dementia among older people

People experiencing homelessness more likely to develop dementia at younger ages, study finds

Can metalens be commercialized at a fraction of the cost?

Reclaim ‘wellness’ from the rich and famous, and restore its political radicalism, new book argues

Curtin research unlocks supernova stardust secrets

New documents reveal patient safety concerns over strike day cover

UTA hosts Solar-bration watch party for April 8 eclipse

Researchers discover molecule that promotes production of cancer cells in triple-negative breast cancer

New tool provides researchers with improved understanding of stem cell aging in the brain

[Press-News.org] First complete coronavirus model shows cooperation
Frontera, Anton 2 supercomputers simulate holistic model of SARS-CoV-2 virion