A computer model developed by Boston College biologists may alter the future of detecting COVID-19 strains by helping to discover new antibodies and cell mutations of the virus, according to Babak Momeni.
“This type of modeling can have many different applications, including finding new antibodies or optimizing antibodies,” Momeni, a researcher on the project and an assistant professor of biology at BC, said.
The BC research team created computerized models of interactions between viruses and their receptors, hopefully allowing scientists to get ahead of the virus, Momeni said.
Marco Zaccaria, a postdoctoral fellow at BC and a researcher on the team, said the team can now provide an estimate of what Omicron mutations could lead to even stronger variants.
“I think we are able to facilitate the identification of the highest affinity antibodies for the actual Omicron variant spike, plus the future most likely changes it may undergo, in an attempt to stay a few steps ahead of the coronavirus evolution,” Zaccaria said.
Momeni said the team used models of atoms, called quantum mechanical modeling, to calculate the electronic structure between molecules and the ways in which they interact.
“One of the aspects of the model is that it looks at individual amino acids and focuses on the role of that amino acid in the interaction between molecules, and that is very helpful for assessing the role of mutations,” Momeni said.
Analyzing amino acids—the molecules that make up proteins—is also beneficial for artificially mutating cell interactions using computer models, according to Momeni. The binding of these molecules and their mutations aids in predicting variants of COVID-19 and other infectious diseases, but there are limitations, Momeni explained.
“Crystal structures tell you where the actual atoms are for a given molecule in space,” Momeni said. “With COVID, we’re lucky enough that a lot of people are working on it and some of these crystal structures were available, but in other cases, there is some work that goes into finding the actual crystal structure [for other infectious diseases].”
One of the major predictions in the biologists’ report, titled “Investigating the Mutational Landscape of the SARS-CoV-2 Omicron Variant Via Ab Initio Quantum Mechanical Modeling,” is how the Omicron variant has stronger binding than previous COVID-19 strains, Momeni said.
“We can identify an additional mutation that could further increase the binding of Omicron to its human receptor,” Momeni said. “And that suggests that there is still room for even stronger binding.”
Prior to the BC biologists’ focus on COVID-19 strains, Momeni said the team worked with French researcher Luigi Genovese on simulating enzymes that break down toxins. Later, when COVID-19 first spread rapidly, the team repurposed its tools to focus on the different variants appearing at the time.
“There was some foundation, but we were looking at other interactions of biological importance,” Momeni said. “It seemed the same tools could be applied to this question and [we] started focusing on that.”
The research team now works in collaboration with the French Alternative Energies and Atomic Energy Commission (CEA). Composed of a group of physicists, including Genovese, the CEA partners provide the actual simulations with supercomputers that run data in a relatively short period of time, Momeni said.
“We collaborate with them to guide them through this process of what would be the right simulations to run and how to analyze data and how to present it so that it would be accessible to biologists,” Momeni said.
Momeni also said that without the physicists’ focus on quantum mechanical simulations, the work would not be possible.
“Our project necessarily relies on the two distinct sets of expertise provided by an evolutionary biologist and a quantum physicist,” Zaccaria said. “The biologist must identify the most insightful questions to drive the scientific investigation, and the physicist must be able to distill the answers from the information that can be mined from ab initio modeling, which is massive.”
Other scientists on the project include Welkin Johnson, chair of BC’s biology department, and Michael Farzan, a professor at Scripps Research.
Next steps for the research team will include focusing on antibody engineering and treatment for other viral diseases, most likely starting with HIV, Zaccaria said.
Momeni expects that the team will work toward validating its model in the future in order to better understand COVID-19 variants’ infectivity.
“So as new variants will show up, it will be ongoing work to simulate those structures and confirm that our model is in agreement with what we can see experimentally in terms of what the role that each mutation is,” Momeni said.
Featured Image by Nicole Vagra / Heights Editor
