Ruth Nussinov | |
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Alma mater | University of Washington, Rutgers University |
Known for | Nucleic acid structure prediction, PLoS Computational Biology, Nussinov plots, Equilibrium unfolding, Protein–protein interaction prediction, Dynamic conformations determine protein function and cell phenotype, Conformational selection and population shift, Dynamic allostery, Current Opinion in Structural Biology |
Awards | |
Scientific career | |
Fields | Bioinformatics, Computational structural biology, Biophysics |
Institutions | Weizmann Institute, Berkeley, Harvard, Tel Aviv University, NCI |
Thesis | Secondary structure analysis of nucleic acids (1977) |
Website | http://ccr.cancer.gov/staff/staff.asp?profileid=6892 |
Ruth Nussinov (Hebrew: פרופסורית רותי נוסינוב) is an Israeli-American biologist born in Rehovot who works as a professor in the Department of Human Genetics, School of Medicine at Tel Aviv University and is the senior principal scientist and principal investigator at the National Cancer Institute, National Institutes of Health.[1] Nussinov is also the editor in chief of the Current Opinion in Structural Biology and formerly of the journal PLOS Computational Biology.[2][3]
In 1978, Nussinov proposed the first dynamic programming approach for nucleic acid secondary structure prediction, this method is now known as the Nussinov algorithm.[4][5]
Her most important discovery was in the 1990s. In 1999 Nussinov published the transformational concept that all conformations preexist—even if the crystal captures only one—and that evolution harnesses their dynamic interconversion for function, dispelling the dogma that only the wild-type shape is relevant.[6][7][8][9] Nussinov suggested a vastly different scenario from the-then dogma of two, “open” and “closed" conformations proposed by Monod, Wyman, and Changeux. She proposed that there is not one folded form, nor two—as they suggested—but many different forms, and in equilibrium, the system keeps jumping between them, and that this barrier-crossing is function. The concept that she suggested is significant since it explained that rather than the ligand inducing a conformational change (as in induced fit), the ligand can select a preexisting (relatively rare, non-minimal energy) conformation in the system that may be better suited to dock it, with minor optimization. It will then bind the ligand, and the equilibrium will keep producing more of this conformation to compensate, which she suggested (also in 1999), is the allosteric effect. This foundational “conformational selection and population shift” idea as an alternative to the “induced fit” text-book model explains the mechanism of molecular recognition. The dynamic shifts among conformations explain catalysis (2000), regulation, kinase activation, and allosteric drugs actions.[9] Her concept was confirmed by innumerable experiments and is now widely established. As Nussinov and others have shown since, this paradigm helps unravel diverse processes as signaling, regulation, and aggregation in amyloid diseases, and oncogenic transformation, contributing to extraordinary advancements in understanding structure and function.[10]
Nussinov has authored over 750 scientific papers with nearing 80,000 citations in Google Scholar, and has given hundreds of invited talks.[11][12] Most recently, she pioneered the connection, on the structural and cellular levels, of cancer and neurodevelopmental disorders asking How can same-gene mutations promote both cancer and developmental disorders?.[13]
A personal scientific overview of her biography has been published in 2018 as “Autobiography of Ruth Nussinov”.[14]