G. Marius Clore

National Institutes of Health


Election Year: 2014
Primary Section: 29, Biophysics and Computational Biology
Secondary Section: 14, Chemistry
Membership Type: Member

Biosketch

Marius Clore is a Distinguished Investigator in the Laboratory of Chemical Physics at the National Institutes of Health (NIH). He is a biophysicist recognized for his pioneering work on the development of NMR for determining three-dimensional solution structures of biological macromolecules and extending the frontiers of NMR to ever more complex systems. His work characterizing the structure and dynamics of sparsely populated, heretofore invisible, states of macromolecules has shed unique insights into macromolecular recognition. Clore was born in London, U.K. in 1955 and became a U.S. citizen in 1996. He grew up in London receiving his undergraduate degree in Biochemistry from University College London, his medical degree from University College Hospital Medical School, London, and his doctorate from the MRC National Institute for Medical Research in London. He joined the scientific staff of the MRC National Institute for Medical Research in 1980, became head of the biological NMR group at the Max-Planck Institute for Biochemistry (Martinsried, Germany) in 1984, and moved to the NIH in 1988. Awards include Membership of the National Academy of Sciences, Fellowship of the Royal Society of Chemistry and the American Academy of Arts and Sciences, the Royal Society of Chemistry Centenary Prize, and the Biochemical Society Centenary Award and Frederick Gowland-Hopkins lecture.

Research Interests

My research is centered upon the development and application of nuclear magnetic resonance (NMR) to study the structure and dynamics of biological macromolecules and their complexes in solution. Particular emphasis is being placed on novel approaches to extending NMR to larger and more complex systems, especially complexes involved in signal transduction and transcriptional regulation, and exploring fundamental questions associated with protein dynamics, macromolecular interactions and recognition processes. Currently we are exploiting the unique properties of NMR to detect and characterize sparsely-populated states of macromolecules. Many important biological processes proceed through transient intermediate states that comprise only a small fraction of the overall population of a molecular system at equilibrium, and, as a result, are invisible (i.e. dark) to conventional biophysical techniques (including crystallography, cryo-electron microscopy and single molecule spectroscopies). These studies, which have provided new insights into macromolecular recognition, rely on the ability of NMR to amplify, through exchange phenomena, the effect of the invisible "dark" state on some NMR observable (generally a relaxation property) so that its footprint is readily observed in measurements on the NMR visible species. Examples of such phenomena that we have studied include the search processes whereby transcription factors locate their specific DNA binding site within an overwhelming sea of non-specific DNA; the role of encounter complexes in protein-protein association; the interplay of conformational selection and induced fit in protein-ligand interactions; and transient interactions of intrinsically disordered and partially folded polypeptides with large megadalton macromolecular assemblies including highly heterogeneous aggregates involved in amyloid protofibril formation.

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