Ruth  Nussinov, Ph.D.

Ruth Nussinov, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Cancer Innovation Laboratory


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. In 1999 she 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’. Our 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 to the groundbreaking “conformational selection and population shift” idea (also published as of 1999) 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. This paradigm impacted the community's views. She suggested that allosteric mutations shift the ensemble in the same way. To date, 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. She applied them to unravel the structural mechanisms of allosteric drug action and formulate determinants of agonist/antagonist drug design. Her group unraveled the detailed oncogenic activation of PI3K, B-Raf, and PTEN and the structural basis for oncogenic Ras signaling at the membrane, also confirmed by experiments, and recently neurodevelopmental disorders in the MAPK and PI3K/mTOR pathways. Her pioneering pivotal concepts contributed to extraordinary advances in understanding the conformational behaviors of biological macromolecules, and their uncontrolled actions in disease. She have advised/co-advised tens of students and postdocs from computer science, engineering, physics, chemistry, genetics, and biology..

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), and the American Institute for Medical and Biological Engineering (AIMBE).  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, "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), Most of her publications are conceptualized and driven by her group.

Recently, we developed KDS (Kinase Drug Selectivity) software for the human kinome,   

A personal scientific overview of her biography has been published in Trends Pharmacol Sci. 2017 Sep;38(9):761-763. doi: 10.1016/

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


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 ]

AlphaFold, Artificial Intelligence (AI), and Allostery

Nussinov R, Zhang M, Liu Y, Jang H
J. Phys. Chem. B. 126/34: 6372-6383, doi: 10.1021/acs.jpcb.2c04346, 2022.
Full-Text Article
[ Journal Article ]

Neurodevelopmental disorders, like cancer, are connected to impaired chromatin remodelers, PI3K/mTOR, and PAK1-regulated MAPK

Nussinov R, Yavuz BR, Arici MK, Demirel HC, Zhang M, Liu Y, Tsai CJ, Jang H, Tuncbag N
Biophys Rev. 15/2: 163-181, doi: 10.1007/s12551-023-01054-9, 2023.
Full-Text Article
[ Journal Article ]

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Liang Xu, Ph.D.
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