G. Marius Clore
G. Marius Clore
Gideon Marius Clore
|Alma mater||University College London and University College Hospital Medical School, London, U.K.|
|Known for||Laying the foundations for three-dimensional protein structure determination in solution by NMR, developing innovative approaches for extending NMR to larger and more complex systems, and using NMR to uncover invisible states of proteins|
|Awards||•Member of the National Academy of Sciences|
•Fellow of the Royal Society
•Fellow of the American Academy of Arts and Sciences
•Foreign Member of the Academia Europaea
•Royal Society of Chemistry Centenary Prize (2011)
•Biochemical Society Centenary Award (2013)
|Fields||Molecular Biophysics, Nuclear Magnetic Resonance, Structural Biology|
|Doctoral advisor||Sir Arnold Burgen FRS|
G. Marius Clore MAE, FRSC, FRS is a British-born, Anglo-American molecular biophysicist and structural biologist. He was born in London, U.K. and is a dual US/U.K. Citizen. He is a Member of the National Academy of Sciences, a Fellow of the Royal Society, a NIH Distinguished Investigator, and the Chief of the Molecular and Structural Biophysics Section in the Laboratory of Chemical Physics of the National Institute of Diabetes and Digestive and Kidney Diseases at the U.S. National Institutes of Health. He is known for his foundational work in three-dimensional protein and nucleic acid structure determination by biomolecular NMR spectroscopy, for advancing experimental approaches to the study of large macromolecules and their complexes by NMR, and for developing NMR-based methods to study rare conformational states in protein-nucleic acid and protein-protein recognition. Clore's discovery of previously undetectable, functionally significant, rare transient states of macromolecules has yielded fundamental new insights into the mechanisms of important biological processes, and in particular the significance of weak interactions and the mechanisms whereby the opposing constraints of speed and specificity are optimized. Further, Clore's work opens up a new era of pharmacology and drug design as it is now possible to target structures and conformations that have been heretofore unseen.
Clore received his undergraduate degree with first class honours in biochemistry from University College London in 1976 and medical degree from University College Hospital Medical School in 1979. After completing house physician and house surgeon appointments at University College Hospital and St Charles' Hospital (part of the St. Mary's Hospital group), respectively, he was a member of the scientific staff of the Medical Research Council National Institute for Medical Research from 1980 to 1984. He received his PhD from the National Institute for Medical Research in Physical Biochemistry in 1982. He was awarded a Lister Institute Research Fellowship from the Lister Institute of Preventive Medicine which he held from 1982 to 1984 at the Medical Research Council. In 1984 he joined the Max Planck Institute for Biochemistry in Martinsried, Germany, where he headed the Biological NMR group from 1984 to 1988.
In 1988, Clore was recruited to the National Institutes of Health (NIH) Laboratory of Chemical Physics (National Institute of Diabetes and Digestive and Kidney Diseases) located in Bethesda, Maryland, U.S.A., where he interacted closely in the late 1980s and early 1990s with NIH colleagues Ad Bax, Angela Gronenborn and Dennis Torchia on the development of multidimensional heteronuclear NMR spectroscopy and a structural biology effort aimed at proteins involved in the pathogenesis of HIV/AIDS. He has remained at the NIH ever since and is currently a NIH Distinguished Investigator and Chief of the Section on Molecular and Structural Biophysics at the NIH. He is an elected Member of the United States National Academy of Sciences, a Fellow of the Royal Society, a Fellow of the American Academy of Arts and Sciences, and a Foreign Member of the Academia Europaea (Biochemistry and Molecular Biology Section). Clore's citation upon election to the Royal Society reads:
"Clore pioneered the development of NMR for determining three-dimensional structures of biological macromolecules and has consistently extended the frontiers of NMR to ever more complex systems. His work on the development of paramagnetic and other relaxation-based NMR experiments to detect and visualize transient, rare states of macromolecules, invisible to conventional structural and biophysical techniques, has shed unique insights into how macromolecules efficiently locate their binding partners, provided the first atomic view of the dynamic amyloid Aß assembly process from disordered peptides into protofibrils, and directly demonstrated that the apo state of the chaperonin GroEL possesses intrinsic foldase/unfoldase activities."
3D structure determination in solution by NMR
Clore played a pivotal role in the development of three- and four-dimensional NMR spectroscopy, the use of residual dipolar couplings for structure determination, the development of simulated annealing and restrained molecular dynamics for three-dimensional protein and nucleic acid structure determination, the solution NMR structure determination of large protein complexes, the development of the combined use of NMR and small-angle X-ray scattering in solution structure determination, and the analysis and characterization of protein dynamics by NMR. Clore's work on complexes of all the cytoplasmic components of the bacterial phosphotransferase system (PTS) led to significant insights into how signal transduction proteins recognize multiple, structurally dissimilar partners by generating similar binding surfaces from completely different structural elements and exploiting side chain conformational plasticity. Clore is also one of the main authors of the very widely used XPLOR-NIH NMR structure determination program
Detection and visualization of excited and sparsely-populated states
Clore's recent work has focused on developing new NMR methods (such as paramagnetic relaxation enhancement, dark state exchange saturation transfer spectroscopy and lifetime line broadening) to detect, characterize and visualize the structure and dynamics of sparsely-populated states of macromolecules, which are important in macromolecular interactions but invisible to conventional structural and biophysical techniques. Examples of include the direct demonstration of rotation-coupled sliding and intermolecular translocation as mechanisms whereby sequence-specific DNA binding proteins locate their target site(s) within an overwhelming sea of non-specific DNA sequences; the detection, visualization and characterization of encounter complexes in protein-protein association; the analysis of the synergistic effects of conformational selection and induced fit in protein-ligand interactions; and the uncovering of "dark", spectroscopically invisible states in interactions of NMR-visible proteins and polypeptides (including intrinsically disordered states) with very large megadalton macromolecular assemblies. The latter includes an atomic-resolution view of the dynamics of the amyloid-β aggregation process. and the demonstration of intrinsic unfoldase/foldase activity of the macromolecular machine GroEL. These various techniques have also been used to uncover the kinetic pathway of pre-nucleation transient oligomerization events and associated structures involving the protein encoded by huntingtin exon-1, which may provide a potential avenue for therapeutic intervention in Huntington's disease, a fatal autosomal dominant, neurodegenerative condition.
Clore is one of the most highly cited scientists in the fields of molecular biophysics, structural biology, biomolecular NMR and chemistry with over 500 published scientific articles and an h-index (number of papers cited h or more time) of 139.
Marius Clore's father was the film producer Leon Clore whose credits include The French Lieutenant's Woman, and his mother was Miriam Clore (née Werner), a member of the Haganah during the 1948 Arab-Israeli War and subsequently the personal assistant to David Ben Gurion prior to moving to England. Sir Charles Clore and Dame Vivien Duffield are his great uncle and second cousin, respectively. He is married to Carole A. Bewley a senior investigator and Chief of the Laboratory of Bioorganic Chemistry in the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health.
Awards and Honors
- 2021: Murray Goodman Memorial Prize
- 2021: Honorary Doctorate of Science (DSc) from University College London
- 2021: Royal Society of Chemistry Khorana Prize
- 2020: Elected Fellow of the Royal Society
- 2020: Biophysical Society Innovation Award
- 2015: Elected Foreign Member of the Academia Europaea.
- 2014: Elected Member of the United States National Academy of Sciences (Biophysics and Computational Biology section)
- 2012: Biochemical Society 2013 Centenary Award (previously known as the Jubilee Medal) and Sir Frederick Gowland Hopkins Memorial Lecture (U.K.)
- 2011: Royal Society of Chemistry Centenary Prize 
- 2011: Elected Fellow of the International Society of Magnetic Resonance
- 2010: Elected Fellow of the American Academy of Arts and Sciences
- 2010: Hillebrand Award of the Washington Chemical Society
- 2009: Elected Fellow of the Biophysical Society
- 2003: Elected Member of the Lister Institute of Preventive Medicine (U.K.)
- 2001: Original member, Institute for Scientific Information (ISI) Highly Cited Researchers Database (in Biology & Biochemistry and Chemistry sections).
- 1999: Elected Fellow of the American Association for the Advancement of Science.
- 1993: Dupont-Merck Young Investigator Award of the Protein Society
- 1990: Elected Fellow of the Royal Society of Chemistry (FRSC) (U.K).
- Samoray C (2016). "Profile of Marius Clore". Proceedings of the National Academy of Sciences of the United States of America. 113 (45): 12604–12606. doi:10.1073/pnas.1616528113. PMC 5111653. PMID 27799541.CS1 maint: uses authors parameter (link)
- Clore, G. Marius. "Curriculum Vitae" (PDF). NIDDK. Retrieved 26 June 2020.
- "American Institute of Physics Oral History Interviews - Marius Clore interviewed by David Zierler". AIP. 24 June 2020. Retrieved 26 June 2020.
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- "G. Marius Clore, MD, Ph.D., NIH Distinguished Investigator". National Institutes of Health Intramural Research Program. Retrieved 14 August 2018.
- "G. Marius Clore, MD, Ph.D., FRS, NIH Distinguished Investigator". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 14 August 2018.
- "New Members and Foreign Associates of the National Academy of Sciences: G. Marius Clore, Gregory C. Fu, Sir J. Fraser Stoddart, Ei-ichi Negishi". Angewandte Chemie International Edition. 53 (26): 6598. 2014. doi:10.1002/anie.201405510.
- Ringe D (1988). "Protein structure: an extra dimension to NMR". Nature. 332 (6162): 303. Bibcode:1988Natur.332..303R. doi:10.1038/332303a0. PMID 3352729. S2CID 32312775.
- Dahlquist FW (2006). "Slip sliding away: new insights into DNA-protein recognition". Nature Chemical Biology. 2 (7): 353–354. doi:10.1038/nchembio0706-353. PMID 16783338. S2CID 12357797.
- Blundell TL, Fernandez-Recio J (2006). "Cell biology: brief encounters bolster contacts". Nature. 444 (7117): 279–280. Bibcode:2006Natur.444..279B. doi:10.1038/nature05306. PMID 17051147. S2CID 4397989.CS1 maint: uses authors parameter (link)
- "Clore named Royal Society Fellow". Retrieved 1 June 2020.
- Deshmukh, L., Tugarinov,V., Appella, D.H., Clore, G.M. (2018). "Targeting a dark excited state of HIV-1 nucleocapsid by anti-retroviral thioesters revealed by NMR spectroscopy". Angewandte Chemie International Edition. 57 (10): 2687–2691. doi:10.1002/anie.201713172. PMC 6034507. PMID 29345807.CS1 maint: uses authors parameter (link)
- "Former Fellows of the Lister Institute of Preventive Medicine". Retrieved 27 June 2020.
- Clore, Marius G (2011). "Adventures in Biomolecular NMR" (PDF). In Harris, Robin K; Wasylishen, Roderick L (eds.). Encyclopedia of Magnetic Resonance. John Wiley & Sons. doi:10.1002/9780470034590. hdl:11693/53364. ISBN 9780470034590.
- "2014 Press release of National Academy of Sciences Members and Foreign Associates Elected". Archived from the original on 2015-08-18.
- "2020 Royal Society press release of outstanding scientists elected as Fellows and Foreign Members".
- "Book of Members, 1780-2014: Chapter B" (PDF). American Academy of Arts and Sciences.
- "American Academy of Arts and Sciences Fellows".
- "Elected Members of Academia Europaea 2015".
- Clore GM, Gronenborn AM (1991). "Structures of larger proteins in solution: three- and four-dimensional heteronuclear NMR spectroscopy". Science. 252 (5011): 1390–1399. Bibcode:1991Sci...252.1390M. doi:10.1126/science.2047852. OSTI 83376. PMID 2047852.CS1 maint: uses authors parameter (link)
- Clore GM (2000). "Accurate and rapid docking of protein-protein complexes on the basis of intermolecular nuclear Overhauser enhancement data and dipolar couplings by rigid body minimization". Proceedings of the National Academy of Sciences USA. 97 (16): 9021–9025. Bibcode:2000PNAS...97.9021C. doi:10.1073/pnas.97.16.9021. PMC 16814. PMID 10922057.CS1 maint: uses authors parameter (link)
- Clore GM, Gronenborn AM (1998). "New methods of structure refinement for macromolecular structure determination by NMR". Proceedings of the National Academy of Sciences of the United States of America. 95 (11): 5891–5898. Bibcode:1998PNAS...95.5891M. doi:10.1073/pnas.95.11.5891. PMC 34492. PMID 9600889.CS1 maint: uses authors parameter (link)
- Clore GM, Venditti V (2013). "Structure, dynamics and biophysics of the cytoplasmic protein-protein complexes of the bacterial phosphoenolpyruvate:sugar phosphotransferase system". Trends in Biochemical Sciences. 38 (10): 515–530. doi:10.1016/j.tibs.2013.08.003. PMC 3831880. PMID 24055245.CS1 maint: uses authors parameter (link)
- Schwieters CD, Clore, GM (2014). "Using small angle solution scattering data in Xplor-NIH structure calculations". Progress in Nuclear Magnetic Resonance Spectroscopy. 80: 1–11. doi:10.1016/j.pnmrs.2014.03.001. PMC 4057650. PMID 24924264.CS1 maint: uses authors parameter (link)
- Clore GM, Driscoll PC, Wingfield PT, Gronenborn AM (1990). "Analysis of backbone dynamics of interleukin-1beta using two-dimensional inverse detected heteronuclear 15N-1H NMR spectroscopy". Biochemistry. 29 (32): 7387–7401. doi:10.1021/bi00484a006. PMID 2223770.CS1 maint: uses authors parameter (link)
- Schwieters CD, Kuszewski JJ, Tjandra N, Clore GM (2003). "The Xplor-NIH NMR molecular structure determination package". Journal of Magnetic Resonance. 160 (1): 65–73. Bibcode:2003JMagR.160...65S. doi:10.1016/S1090-7807(02)00014-9. PMID 12565051.CS1 maint: uses authors parameter (link)
- Anthis NJ, Clore GM (2015). "Visualizing transient dark states by NMR spectroscopy". Quarterly Reviews in Biophysics. 48 (1): 35–116. doi:10.1017/S0033583514000122. PMC 6276111. PMID 25710841.CS1 maint: uses authors parameter (link)
- Iwahara J, Clore GM (2006). "Detecting transient intermediates in macromolecular binding by paramagnetic NMR". Nature. 440 (7088): 1227–1230. Bibcode:2006Natur.440.1227I. doi:10.1038/nature04673. PMID 16642002. S2CID 4427016.CS1 maint: uses authors parameter (link)
- Tang C, Iwahara J, Clore GM (2006). "Visualization of transient encounter complexes in protein-protein association". Nature. 444 (7117): 383–386. Bibcode:2006Natur.444..383T. doi:10.1038/nature05201. PMID 17051159. S2CID 4422087.CS1 maint: uses authors parameter (link)
- Tang C, Schwieters CD, Clore GM (2007). "Open-to-closed transition in apo-maltose-binding protein visualized by paramagnetic NMR". Nature. 449 (7165): 1078–1082. Bibcode:2007Natur.449.1078T. doi:10.1038/nature06232. PMID 17960247. S2CID 4362128.CS1 maint: uses authors parameter (link)
- "NMR advance brings proteins into the open". Neurosciencenews.com. 25 June 2013.
- Fawzi NL, Ying J, Ghirlando R, Torchia DA, Clore GM (2011). "Atomic resolution dynamics on the surface of amyloid beta protofibrils probed by solution NMR". Nature. 480 (7376): 268–272. Bibcode:2011Natur.480..268F. doi:10.1038/nature10577. PMC 3237923. PMID 22037310.CS1 maint: uses authors parameter (link)
- Libich, D.S., Tugarinov, V., Clore, G.M. (2015). "Intrinsic unfoldase/foldase activity of the chaperonin GroEL directly demonstrated using multinuclear relaxation-based NMR". Proc. Natl. Acad. Sci. U.S.A. 112 (29): 8817–8823. Bibcode:2015PNAS..112.8817L. doi:10.1073/pnas.1510083112. PMC 4517251. PMID 26124125.CS1 maint: uses authors parameter (link)
- Kotler, S.A., Tugarinov, V., Schmidt, T., Ceccon, A., Libich, D.S., Ghirlando, R., Schwieters, C.D., Clore, G.M. (2019). "probing the initial transient oligomerization events facilitating Huntingtin fibril nucleation at atomic resolution by relaxation-based NMR". Proc. Natl. Acad. Sci. U.S.A. 116 (9): 3562–3571. doi:10.1073/pnas.1821216116. PMC 6397591. PMID 30808748.CS1 maint: uses authors parameter (link)
- Ceccon, A., Tugarinov, V., Ghirlando, R., Clore, G.M. (2020). "Abrogation of prenucleation, transient oligomerization of the huntingtin exon-1 protein by human profilin". Proc. Natl. Acad. Sci. U.S.A. 117 (11): 5844–5852. doi:10.1073/pnas.1922264117. PMC 7084121. PMID 32127471.CS1 maint: uses authors parameter (link)
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- "Google scholar profile".
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- G. Marius Clore laboratory homepage
- Listing on the United States National Academy of Sciences web site
- Listing on the Royal Society web site
- Listing on the American Academy of Arts and Sciences web site
- Listing on the Academia Europaea web site
- Listing on NIDDK/NIH web site
- Listing on NIH Intramural Research Program web site
- Listing on ResearchGate
- Listing on Google Scholar
- Marius Clore on Landmark Article in the Journal of Magnetic Resonance
- Marius Clore Lecture on "Transient Prenucleation Oligomerization of Huntingtin" at the ICMRBS Webinar on Emerging Topics in Biomolecular Resonance (4/15/2021)
- List of Fellows of the Royal Society elected in 2020
- List of Fellows of the Royal Society
- List of University College London Honorary Graduates
- Notable alumni of UCL Medical School
- Notable alumni of University College London
- Notable Staff of the MRC National Institute for Medical Research, London
- Notable Lister Institute Research Fellows of the Lister Institute for Preventive Medicine
- Notable NIDDK Intramural Scientists Elected to the United States National Academy of Sciences
- Notable alumni of the Lycee Francais Charles de Gaulle London
- List of University College London people
- List of University of London people
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