Ruth Nussinov, Ph.D., who discovered that dynamic ensembles are the true workhorses of cellular function and who has published numerous foundational studies in biophysics and computational biology over the years, was among 120 individuals recently elected to the National Academy of Sciences.
Nussinov, a member of the Basic Science Program at the Frederick National Laboratory for Cancer Research and head of the Computational Structural Biology Section, was also among a dozen women featured in the inaugural issue of Pioneers in Molecular Biology.
The journal highlights outstanding novel discoveries and scientific advancements by women who have demonstrated “courage, strength, and ability to forge opportunities for others who may be interested in pursuing careers in science.” Each of the featured scientists wrote a first-person account of their background and scientific work.
Nussinov said her father’s influence as an agriculture professor and dean at the Hebrew University in Jerusalem (HUJI) sparked her own interest in academia.
“He was studying in his den after long days of working and advising farmers in the field," Nussinov said. "He was revered by colleagues and students. It was this influence, coupled with my aunt being a microbiologist, which led me…to study microbiology in HUJI.”
She continued her undergraduate work at the University of Washington in Seattle where she studied organic and biochemistry, learning how amino-acid and nucleotide units determine 3D molecular structure.
“While I did not realize it at the time, the basic motif of sequence (information) translating into structure, or an ordered pattern, became the guiding principle of my entire scientific career,” she said.
After an eight-year career break to rear three children, she returned to science at a time when DNA sequencing methods were new. Her Ph.D. thesis advisor suggested that Nussinov develop a method to computationally predict the planar, secondary structures of single-stranded RNA molecules.
“I liked it and whole-heartedly devoted myself to it,” she said.
For this, she developed the 0(n3) dynamic programming algorithm for predicting RNA secondary structure, a method now known as the “Nussinov algorithm.” She went on to co-develop a powerful computer vision-based docking algorithm and later proposed the foundational role of conformational ensembles in molecular recognition and allostery.
“Dynamic conformational ensemble shifts are now acknowledged as the origin of recognition, allostery, and signaling, underscoring that conformational ensembles – not proteins – are the workhorses of the cell,” she said. “The new concepts that we have contributed have changed the way biophysicists and structural biologists think...with beneficial and inspiring applications relevant to health, such as cancer and inflammation.”
More recently, Nussinov has collaborated on mechanistic studies relevant to the National Cancer Institute’s RAS Initiative at FNL, where scientists are making progress on a family of mutant genes that drive more than 30 percent of all cancers. In 2020, Nussinov was elected as a fellow of the American Physical Society.
“My work is largely my hobby,” she said, and added that she enjoys immensely the rare privilege of academic freedom to pursue any line of research that she wants.
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