Ruth Nussinov is a biologist by training. Her dissertation proposed the dynamic programming algorithm for predicting the secondary structure of single stranded RNA. It is still the leading method for RNA folding to this date. In 1999 her group proposed the landmark concept that all possible protein conformations preexist, and that evolution has exploited them for function. At the time it was believed that a protein only has two conformations, ‘open’ and ‘closed’. The concept is significant since it explained that rather than the ligand ‘inducing’ a conformational change, the ligand can ‘select’ a preexisting conformation that fits it. This led her group to the groundbreaking “conformational selection and population shift” idea as an alternative to the “induced fit” text-book model to explain the mechanism of molecular recognition. In turn, this implied that following binding of the ligand, there will be a ‘shift of the population’ toward the more stable bound conformation, that is, there will be a redistribution of the ensemble, to maintain its chemical equilibrium. Her biological outlook viewed the free energy landscape in terms of function, making her suggest that this ‘shift’ is the origin of the allosteric effect, and that this is how allostery impacts function. To date, research on molecular recognition, mutations, and allosteric pathways follow this paradigm. She further proposed that the ability to perform biological function is determined by how stable, or populated, a protein is in its active (ON) conformation. In line with this, she suggested that activation by oncogenic mutations mimic the activation mechanism of the wild-type protein. Data over two decades supported these fundamental concepts. Her pioneering pivotal concepts contributed to extraordinary advances in understanding the conformational behaviors of biological macromolecules, and their uncontrolled actions in disease. She won multiple domestic and international awards and accolades, served in multiple editorial roles, advised/co-advised tens of students and postdocs from computer science, engineering, physics, chemistry, mathematics, genetics, and biology. She received her Ph.D. from Rutgers University, postdoc’ed in Structural Chemistry at the Weizmann Institute, was at the Chemistry Department at Berkeley, the Biochemistry Department at Harvard, and a visiting scientist at the NIH. She joined the Medical School at Tel Aviv University where she was a Professor and the Frederick National Laboratory for Cancer Research.
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