Ruth  Nussinov, Ph.D.

Ruth Nussinov, Ph.D.

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


Nussinov pioneered the “conformational selection and population shift” (1999) as an alternative to the “induced fit” text-book model to explain the molecular mechanism of recognition and postulated that population shift underlies allosteric regulation. She proposed that all conformations pre-exist and extended this pre-existing ensemble model to catalysis (2000). In 1999 she also postulated that in both allosteric and non-allosteric binding, the deceptively rigid snapshot images of protein motion observed by crystallography can be explained by the presence of low barriers around the bottom of the funnel and shifts in chemical equilibrium in favor of the bound states. She further posited that activation by oncogenic mutations mimic the activation mechanism of the wild-type protein. Experimental data over two decades supported these fundamental concepts, and as evidenced in the literature, by now a vast number of experimental and computational studies take them as established facts. Nussinov further applied these concepts to unravel the structural mechanisms of allosteric drug action and to formulate determinants of agonist/antagonist drug design. More recently, her group unraveled the detailed oncogenic activation of PI3K, B-Raf, and PTEN and the structural basis for oncogenic Ras signaling, also confirmed by experiments. Her pioneering work has contributed to extraordinary advances in understanding the conformational behaviors of biological macromolecules, and their uncontrolled actions in disease.

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 twice 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"). Most of her publications are conceptualized and driven by her group.

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

1) protein structure, dynamics and function 2) signaling 3) allosteric drugs 4) cellular networks 5) key oncogenic proteins 6) computational biology


Selected Recent Publications

The mechanism of activation of MEK1 by B-Raf and KSR1

Maloney RC, Zhang M, Liu Y, Jang H, Nussinov R.
Cell Mol Life Sci.. May 4;79(5): 281, doi: 10.1007/s00018-022-04296-0., 2022.
Full-Text Article
[ Journal Article ]

Allostery, and how to define and measure signal transduction

Nussinov R, Tsai CJ, Jang H.
Biophys Chem. . Apr: 283, doi: 10.1016/j.bpc.2022.106766., 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. . Jan 14;8(2): eabm2059, doi: 10.1126/sciadv.abm2059., 2022.
Full-Text Article
[ Journal Article ]

The mechanism of Raf activation through dimerization

Zhang M, Maloney R, Jang H, Nussinov R.
Chem Sci. . May 30;25(6): 104492, doi: 10.1016/j.isci.2022.104492. , 2021.
Full-Text Article
[ Journal Article ]

Neurodevelopmental disorders, immunity, and cancer are connected

Nussinov R, Tsai CJ, Jang H.
iScience. May 30;25(6): 104492, doi: 10.1016/j.isci.2022.104492. , 2022.
Full-Text Article
[ Journal Article ]

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Senior Computational Scientist (Contr.)
Hyunbum Jang, Ph.D.
Predoctoral Visiting Fellow (Graduate Student)
Tsung-Jen Liao
Postdoctoral Fellow (Visiting) (Contr.)
Hansaim Lim, Ph.D.
Postdoctoral Fellow (CRTA)
Ryan Maloney, Ph.D.
Guest Researcher (Contr.)
Emine Ozdemir
Guest Researcher (Contr.)
Amarda Shehu, Ph.D.
Programmer/Analyst IV (Contr.)
Chung-Jung Tsai, Ph.D.
Computational Scientist (Contr.)
Mingzhen Zhang, Ph.D.