Research in this laboratory is centered around solution studies on the structure and dynamics of proteins, protein-protein complexes and protein-nucleic acid complexes using multidimensional NMR spectroscopy, and on the development and application of novel NMR and computational methods to aid in these studies. Over the last year we have developed several new multidimensional pulse sequences to derive assignments using direct-carbon detect methods;multidimensional sequences to detect arginine guanidino and lysine NH3 groups;new approaches to docking protein-protein complexes based on very sparse intermolecular NOE data;various computational approaches to facilitate structure determination and automation;and we have solved the structures of several large protein-protein complexes, including a phosphoryl transfer complexes of enzymes IIAMannitol and IIBMannitol, IIAmannose and IIBMannose, IIAChitobiose-IIBChitobiose from the bacterial phosphoryl transfer system. In addition, we have devoted significant efforts towards detecting, characterizing and visualizing highly transient, lowly-populated states that are invisible to conventional biophysical and structural techniques, yet play a key role in numerous biological processes including recognition, allostery, signal transduction, etc.... by means of paramagnetic relaxation enhancement (PRE) methods. Using this approach we have been able to characterize the initial stages invlved in autoprocessing of HIV-1 protease.

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Ceccon, Alberto; Schmidt, Thomas; Tugarinov, Vitali et al. (2018) Interaction of Huntingtin Exon-1 Peptides with Lipid-Based Micellar Nanoparticles Probed by Solution NMR and Q-Band Pulsed EPR. J Am Chem Soc 140:6199-6202
Deshmukh, Lalit; Tugarinov, Vitali; Appella, Daniel H et al. (2018) Targeting a Dark Excited State of HIV-1 Nucleocapsid by Antiretroviral Thioesters Revealed by NMR Spectroscopy. Angew Chem Int Ed Engl 57:2687-2691
Wälti, Marielle A; Libich, David S; Clore, G Marius (2018) Extensive Sampling of the Cavity of the GroEL Nanomachine by Protein Substrates Probed by Paramagnetic Relaxation Enhancement. J Phys Chem Lett 9:3368-3371
Schmidt, Thomas; Tian, Lan; Clore, G Marius (2018) Probing Conformational States of the Finger and Thumb Subdomains of HIV-1 Reverse Transcriptase Using Double Electron-Electron Resonance Electron Paramagnetic Resonance Spectroscopy. Biochemistry 57:489-493
Wälti, Marielle A; Clore, G Marius (2018) Disassembly/reassembly strategy for the production of highly pure GroEL, a tetradecameric supramolecular machine, suitable for quantitative NMR, EPR and mutational studies. Protein Expr Purif 142:8-15
Ceccon, Alberto; Tugarinov, Vitali; Boughton, Andrew J et al. (2017) Probing the Binding Modes of a Multidomain Protein to Lipid-based Nanoparticles by Relaxation-based NMR. J Phys Chem Lett 8:2535-2540
Schwieters, Charles D; Bermejo, Guillermo A; Clore, G Marius (2017) Xplor-NIH for Molecular Structure Determination from NMR and Other Data Sources. Protein Sci :
Libich, David S; Tugarinov, Vitali; Ghirlando, Rodolfo et al. (2017) Confinement and Stabilization of Fyn SH3 Folding Intermediate Mimetics within the Cavity of the Chaperonin GroEL Demonstrated by Relaxation-Based NMR. Biochemistry 56:903-906
Deshmukh, Lalit; Tugarinov, Vitali; Louis, John M et al. (2017) Binding kinetics and substrate selectivity in HIV-1 protease-Gag interactions probed at atomic resolution by chemical exchange NMR. Proc Natl Acad Sci U S A 114:E9855-E9862
Wälti, Marielle A; Schmidt, Thomas; Murray, Dylan T et al. (2017) Chaperonin GroEL accelerates protofibril formation and decorates fibrils of the Het-s prion protein. Proc Natl Acad Sci U S A 114:9104-9109

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