G. Marius Clore

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G. Marius Clore
Structural Biology, Chemistry
Institutions
Doctoral advisorSir Arnold Burgen FRS
Notable students
Websitegmclore.org/clore

G. Marius Clore

protein-protein[11] recognition.[12] 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.[13]

Biography

Clore received his undergraduate degree with

Max Planck Institute for Biochemistry in Martinsried, Germany, where he headed the Biological NMR department from 1984 to 1988.[1][2]

In 1988, Clore was recruited to the

United States National Academy of Sciences,[16] a Fellow of the Royal Society,[17] a Fellow of the Academy of Medical Sciences, a Fellow of the American Academy of Arts and Sciences,[18][19] and a Foreign Member of the Academia Europaea (Biochemistry and Molecular Biology Section).[20] 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."[5]

Research

3D structure determination in solution by NMR

Clore played a pivotal role in the development of three- and four-dimensional NMR spectroscopy,[21] the use of residual dipolar couplings for structure determination,[22] the development of simulated annealing and restrained molecular dynamics for three-dimensional protein and nucleic acid structure determination,[23] the solution NMR structure determination of large protein complexes,[24] the development of the combined use of NMR and small-angle X-ray scattering in solution structure determination,[25] and the analysis and characterization of protein dynamics by NMR.[26] 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.[24] Clore is also one of the main authors of the very widely used XPLOR-NIH NMR structure determination program[27]

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.[28] 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;[29] the detection, visualization and characterization of encounter complexes in protein-protein association;[30] the analysis of the synergistic effects of conformational selection and induced fit in protein-ligand interactions;[31] 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.[32] The latter includes an atomic-resolution view of the dynamics of the amyloid-β aggregation process.[33] and the demonstration of intrinsic unfoldase/foldase activity of the macromolecular machine GroEL.[34] 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.[35][36]

Scientific impact

Clore is one of the most highly cited scientists in the fields of molecular biophysics, structural biology, biomolecular NMR and chemistry

Harold Varmus and Ad Bax
.

Personal life

Marius Clore was educated at the

Lycee Francais Charles de Gaulle in Kensington, London, University College London and UCL Medical School. He holds a 3rd degree black belt in Tae Kwon Do and was an avid cave diver. Marius Clore's father was the film producer Leon Clore whose credits include The French Lieutenant's Woman
.

Awards and honors

References

  1. ^
    PMID 27799541
    .
  2. ^ a b Clore, G. Marius. "Curriculum Vitae" (PDF). NIDDK. Retrieved 26 June 2020.
  3. ^ "American Institute of Physics Oral History Interviews - Marius Clore interviewed by David Zierler". AIP. 24 June 2020. Retrieved 26 June 2020.
  4. ^ a b c d "G. Marius Clore". Member Directory. National Academy of Sciences. Retrieved 12 March 2015.
  5. ^ a b c "G. Marius Clore". Member Directory. Royal Society. Retrieved 29 April 2020.
  6. ^ "G. Marius Clore, MD, Ph.D., NIH Distinguished Investigator". National Institutes of Health Intramural Research Program. Retrieved 14 August 2018.
  7. ^ "G. Marius Clore, MD, Ph.D., FRS, NIH Distinguished Investigator". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 14 August 2018.
  8. doi:10.1002/anie.201405510
    .
  9. S2CID 32312775
    .
  10. S2CID 12357797
    .
  11. S2CID 4397989
    .
  12. ^ "Clore named Royal Society Fellow". Retrieved 1 June 2020.
  13. PMID 29345807
    .
  14. ^ a b "Former Fellows of the Lister Institute of Preventive Medicine". Retrieved 27 June 2020.
  15. ISBN 978-0-470-03459-0. Archived from the original
    (PDF) on 2016-03-05. Retrieved 2015-03-14.
  16. ^ "2014 Press release of National Academy of Sciences Members and Foreign Associates Elected". Archived from the original on 2015-08-18.
  17. ^ "2020 Royal Society press release of outstanding scientists elected as Fellows and Foreign Members".
  18. ^ a b "Book of Members, 1780-2014: Chapter B" (PDF). American Academy of Arts and Sciences.
  19. ^ a b "American Academy of Arts and Sciences Fellows".
  20. ^ a b "Elected Members of Academia Europaea 2015".
  21. PMID 2047852
    .
  22. PMID 10922057
    .
  23. PMID 9600889
    .
  24. ^
    PMID 24055245
    .
  25. PMID 24924264
    .
  26. PMID 2223770
    .
  27. PMID 12565051
    .
  28. PMID 25710841
    .
  29. S2CID 4427016
    .
  30. S2CID 4422087
    .
  31. S2CID 4362128
    .
  32. ^ "NMR advance brings proteins into the open". Neurosciencenews.com. 25 June 2013.
  33. PMID 22037310
    .
  34. PMID 26124125
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  35. PMID 30808748
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  36. PMID 32127471
    .
  37. ^ "Top 10 researchers in chemistry based on total citations". Times Higher Education. 9 October 2008.
  38. ^ "Royal Society of Chemistry h-index ranking of living chemists" (PDF).
  39. ^ "Google scholar profile".
  40. ^ "Academy of Medical Sciences announces new Fellows of 2024".
  41. ^ "G. Marius Clore 2021 Murray Goodman Memorial Prize Winner".
  42. ^ "UCL Awards 2021 Honorary Degrees and Fellowships". 15 July 2021.
  43. ^ "G. Marius Clore 2021 Royal Society of Chemistry Khorana Prize Winner".
  44. ^ "G. Marius Clore to Receive Biophysical Society 2020 Innovation Award".
  45. ^ "Biophysical Society September 2019 Press Release".
  46. ^ "Biochemical Society Award Winners for 2013 - Biochemist e-volution" (PDF). Biochemical Society.
  47. ^ "The Centenary Award". biochemistry.org.
  48. ^ "Centenary Prize Winner 2011". rsc.org.
  49. ^ "List of elected ISMAR fellows". Archived from the original on 2015-10-27.
  50. ^ "Chemical Society of Washington Hillebrand Award". Archived from the original on 2011-03-06. Retrieved 2015-03-09.
  51. ^ "American Society of Biochemistry and Molecular Biology Today, May 2011, ASBMB member update p. 6" (PDF).
  52. ^ "Fellow of the Biophysical Society Award". biophysics.org.
  53. ^ "Members/Former Fellows". lister-institute.org.uk. Archived from the original on 2015-08-05. Retrieved 2015-02-19.
  54. ^ "Fellows of the American Associastion for the Advancement of Science".
  55. ^ "Protein Society Young Investigator Award". Archived from the original on 2015-02-14. Retrieved 2015-02-19.
  56. ^ "NIDDK scientists share award" (PDF). The NIH Record (1993) volume 45(17), page 12.
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