G. Marius Clore MAE, FRSC, FMedSci, FRS is a British and American molecular biophysicist and structural biologist. He was born in London, U.K. and is a dual U.S./U.K. Citizen. He is a Member of the National Academy of Sciences, a Fellow of the Royal Society, a Fellow of the Academy of Medical Sciences, a Fellow of the American Academy of Arts and Sciences, 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.
Biography Clore received his undergraduate degree with first class honours in biochemistry from University College London in 1976 and medical degree from UCL 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 joint 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 department 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., 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 Academy of Medical Sciences, 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."
Research
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
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