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Ruth  Nussinov, Ph.D.

Ruth Nussinov, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Senior Investigator (Contr)
Cancer Innovation Laboratory
Head, Computational Structural Biology Section

RESEARCH SUMMARY

Dr. 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.

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. 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.  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. Her pioneering work has contributed to extraordinary advances in understanding the conformational behaviors of biological macromolecules, their uncontrolled actions in disease, and form the basis for allosteric drug actions.

Dr. Nussinov served as the Editor-in-Chief of PLOS Computational Biology and is currently Editor-in-Chief of Current Opinion in Structural Biology.  She is an elected Fellow of the Biophysical Society, the International Society of Computational Biology (ISCB), the American Physical Society (APS), the American Institute for Medical and Biological Engineering (AIMBE), and EMBO Fellow.  She was recognized by multiple Domestic and International Awards. She has been designated multiple times a Highly Cited Researcher (ranking among the top 3000 researchers or 1% across all fields according to Thomson Reuters Essential Science Indicators, http://highlycited.com/ "earning them the mark of exceptional impact"). and her impact among the top female scientists was ranked as 44 in the US (66 world-wide), https://research.com/scientists-rankings/best-female-scientists. Most of her publications are conceptualized and driven by her group.

Recently, we developed KDS (Kinase Drug Selectivity) software for the human kinome, https://github.com/CBIIT/KDS.   

A personal scientific overview of her biography has been published in

 http://www.sciencedirect.com/science/article/pii/S0165614717301293?via%3Dihub Trends Pharmacol Sci. 2017 Sep;38(9):761-763. doi: 10.1016/j.tips.2017.06.008.

Autobiography of Ruth Nussinov.
Nussinov R. J Phys Chem B. 2021 Jul 1;125(25):6735-6739. doi:10.1021/acs.jpcb.1c04719

Areas of Expertise

Protein Structure Dynamics and Function
Allosteric Drugs
Key Oncogenic Proteins

Publications

Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance

Nussinov R, Jang H
Annu Rev Pharmacol Toxicol. doi: 10.1146/annurev-pharmtox-022823-113946, 2024.
Full-Text Article
[ Journal Article ]

A new view of activating mutations in cancer

Nussinov R, Tsai CJ, Jang H
Cancer Res. 82/22: 4114-4123, doi: 10.1158/0008-5472.CAN-22-2125, 2022.
Full-Text Article
[ Journal Article ]

How can same-gene mutations promote both cancer and developmental disorders?

Nussinov R, Tsai CJ, Jang H
Sci Adv. 8/2: eabm2059, doi: 10.1126/sciadv.abm2059, 2022.
Full-Text Article
[ Journal Article ]

Mitogen signaling strength and duration can control cell cycle decisions

Nussinov R, Zhang W, Liu Y, Jang H.
Sci. Adv. . 10(27): eadm9211, 2024.
Full-Text Article
[ Journal Article ]

Anticancer drugs: How to select small molecule combinations?

Nussinov R, Yavuz BR, Jang H.
Trends Pharmacol. Sci. . 45(6): 503-519, 2024.
Full-Text Article
[ Journal Article ]

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Team

Senior Computational Scientist (Contr.)
Hyunbum Jang, Ph.D.
Computational Scientist (Contr.)
Liang Xu, Ph.D.
Postdoctoral Fellow (CRTA)
Yonglan Liu, Ph.D.
Research Fellow
Wengang Zhang, Ph.D.
Postdoctoral Fellow (CRTA)
Bengi Ruken Yavuz, Ph.D.
Postdoctoral Fellow (CRTA)
Clil Regev, Ph.D.
Guest Researcher (Contr.)
Nurit Haspel, Ph.D.
Guest Researcher (Contr.)
Amarda Shehu, Ph.D.
VOLUNTEER
Michael Bergman
VOLUNTEER
Janka Czigléczki
Guest Researcher (Contr.)
Simge Senyuz
Guest Researcher (Contr.)
Kayra Kosoglu
Guest Researcher (Contr.)
Meryem Eren
Guest Researcher (Contr.)
Fatma Cankara
Guest Researcher (Contr.)
Zeynep Abali
Guest Researcher (Contr.)
Damla Ovek
Guest Researcher (Contr.)
H. Cansu Demirel
Guest Researcher (Contr.)
Zeynep Aydin
GUEST RESEARCHER (Contr.)
M.Kaan Arici