Ada Sedova: Building a supercomputing platform for biological discovery

  • Computational biophysicist Ada Sedova is using experiments and high-performance computing to explore the properties of biological systems and predict their form and function, including research to accelerate drug discovery for COVID-19. Photo credit: Jason Richards, Oak Ridge National Laboratory, U.S. Dept. of Energy.

    Computational biophysicist Ada Sedova is using experiments and high-performance computing to explore the properties of biological systems and predict their form and function, including research to accelerate drug discovery for COVID-19. Photo credit: Jason Richards, Oak Ridge National Laboratory, U.S. Dept. of Energy.

  • Computational biophysicist Ada Sedova is using experiments and high-performance computing to explore the properties of biological systems and predict their form and function, including research to accelerate drug discovery for COVID-19. Photo credit: Jason Richards, Oak Ridge National Laboratory, U.S. Dept. of Energy.

    Ada Sedova uses experiments and computing to explore the properties of biological systems and predict their form and function.

  • Computational biophysicist Ada Sedova is using experiments and high-performance computing to explore the properties of biological systems and predict their form and function, including research to accelerate drug discovery for COVID-19. Photo credit: Jason Richards, Oak Ridge National Laboratory, U.S. Dept. of Energy.

    Computational biophysicist Ada Sedova is using experiments and high-performance computing to explore the properties of biological systems and predict their form and function, including research to accelerate drug discovery for COVID-19. Photo credit: Jason Richards, Oak Ridge National Laboratory, U.S. Dept. of Energy.

  • Computational biophysicist Ada Sedova is using experiments and high-performance computing to explore the properties of biological systems and predict their form and function, including research to accelerate drug discovery for COVID-19. Photo credit: Jason Richards, Oak Ridge National Laboratory, U.S. Dept. of Energy.

    Ada Sedova uses experiments and computing to explore the properties of biological systems and predict their form and function.

Ada Sedova’s journey to Oak Ridge National Laboratory has taken her on the path from pre-med studies in college to an accelerated graduate career in mathematics and biophysics and now to the intersection of computational science and biology. Through it all, her math and science prowess, insatiable curiosity and personal drive have propelled her to a moment when her expertise in computational biophysics is supporting a wide range of research, from a better understanding of plant biology for the production of biofuels and biproducts, to the search for therapeutics to treat COVID-19.

Sedova’s research spans multiple disciplines from biology, chemistry, mathematics and physics to analyze the molecular workings of biological systems and better understand how genes affect the physical traits of everything from plants to microbes, including pathogens. In a project focused on complex biosystems, she is bringing together data to create a high-performance computational platform to translate genetic code into function. Other work focuses on computational work for biosecurity, creating tools to predict unintended effects of gene editing across ecosystems, such as targeting a fungal pest that can adversely affect the Populus biomass feedstock crop.

In research launched this spring, Sedova is accelerating a suite of computational tools for molecular modeling on the Summit supercomputer at ORNL. The tools will speed our understanding of how viruses such as the SARS-CoV-2 coronavirus and other microbes interact with drug molecules. The results will help equip a national high-performance computing consortium of government, industry, and academic researchers.

The need for HPC in biology is spurred by the massive amount of data now available due to faster and cheaper genome sequencing, Sedova noted. “We’re suddenly dealing with the size of data that astrophysicists deal with, all because of the genome sequencing revolution,” she said. “We want to be able to use HPC to take that sequencing data and come up with useful inferences. We want to quickly answer questions such as ‘what does this protein do, and how does it affect the cell? How can we harness biomolecules based on the genetic information we have?'”

The speeds the simulations have reached just in the past few months on the Summit system are “unbelievable,” Sedova said. “The fastest these codes have ever run.” The work supports molecular simulations and protein docking investigations for drug discovery now, and in the long run scientists hope to add in mutation analysis-looking at how a virus may change using computational evolution analysis. “It could be possible that as a protein mutates then the drugs we’re using may not bind as well anymore. We want to look ahead and incorporate these ideas into a drug discovery pipeline that predicts possible drug resistance,” she explained.

Long-term, Sedova envisions a biology-focused HPC effort at ORNL, with the capability to rapidly accelerate our knowledge about biological systems that affect everything from the bioeconomy to global health. The work will evolve as the tools change, including the advancement to exascale computing with the Frontier system being built at ORNL, expected to exceed a quintillion, or 1018, calculations per second. She is already involved in the early work to adapt biology codes to the exascale environment.

Sedova’s research can feel all-encompassing these days, as the importance of the COVID-19 fight, along with other ongoing projects, equate to long days of work. But she has a deep well of determination to see her through.

Doubling up at UNC Asheville

Sedova attended the University of North Carolina Asheville as an undergraduate, earning a bachelor’s degree with a double major in pre-med and math and a double minor in biology and French.

While there, she would read medical literature in the college’s library for hours. “I was very excited about what I was reading; it felt almost like being a detective. I was very interested in figuring things out-putting evidence together. It made me realize that I might want to consider a career in the research space,” she said.

Sedova moved to New York to pursue a master’s degree in mathematics and to learn more about the math used in quantum mechanics and chemistry at the University at Albany. At Albany, while considering whether to go to medical school or pursue a doctorate in research, she found her true calling while taking biomedical science classes. Her skills in quantum mathematics, biomedicine and biology led her to being recruited to pursue a doctorate in biomedical science, with a concentration in computational biophysics and structural biology. She studied in a joint program between U-Albany and the New York State Department of Health’s Wadsworth Center, one of the oldest human health research institutions in the country.

Sedova earned both her master’s and doctoral degrees within five years, and ended up defending both of those theses in the same semester toward the end of her studies.

With her degrees newly in hand, she worked at the U-Albany Department of Chemistry as a postdoctoral researcher focused on analytical bioelectrochemistry and genetic biosensors, performing both computational work modeling the fluid flow in a genetic sensing assay as well as experimental work creating new biosensors in the lab. She was then recruited for a postdoctoral position by the Scientific Computing Group at the National Center for Computational Sciences at ORNL.

A return to the Appalachian foothills

“I interviewed at the lab in the spring and everything was just beautiful on the main campus. I realized how much I’d missed the Southern Appalachians,” Sedova said. She spent three years as a postdoc, working on the Oak Ridge Leadership Computing Facility’s supercomputers and conducting research at the Spallation Neutron Source. Both the OLCF and SNS are U.S. Department of Energy Office of Science user facilities at ORNL.

Her research used neutrons to explore intermolecular interactions in bio-organic and organic molecules. These interactions form the basis of molecular recognition that is critical to biochemical and cellular processes, but which are difficult to describe computationally. She conducted experimental work on the VISION instrument and the neutron reflectometer at SNS, and used the OLCF supercomputers to simulate and interpret experimental measurements.

Now as a researcher in ORNL’s Biosciences Division. Sedova views the long-term impact of her work clearly. “If we can come up with an HPC simulation factory to predict function from structure, or even function from gene sequences, we can make an enormous difference in the areas of biotechnology, biosecurity, bioenergy and even climate change. We can more accurately manipulate plants and microorganisms to be more hardy-increasing carbon upcycling to reduce carbon in the atmosphere, for instance,” she explained.

Sedova doesn’t see her work slowing down any time soon, especially as the computational biology pipeline is still growing at ORNL, and the COVID-19 research remains urgent. She hopes to eventually have time to return to her early bioelectrochemistry research with neutrons and to add nucleic acid simulation and experimentation to her roster in the biosciences organization.

Her biggest challenge so far at the lab has been upgrading biology codes-typically unsuited for HPC-to run on Summit, as well as adapting deep learning techniques in a supercomputing environment. Her biggest success, she says, is the COVID-19 work, particularly the incredible collaboration that has happened in the search for successful treatments. “It shows that when everyone is working together, with support from the biosciences organization, OLCF and even outside vendors like NVIDIA who helped upgrade code for use on the Summit GPUs, we can be very successful. I have so many great colleagues to work with in multiple disciplines with incredible resources at ORNL.”

Sedova says what drives her work is a natural inquisitiveness, which took root in the college library and continues today. “I have to know ‘why,’ and that’s why research works for me,” she said. “I feel blessed in my life to finally get to a place where I’m doing something that I enjoy absolutely every minute of.”

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