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 novel hybrid methods combining NMR and solution scattering to solve the structures of proteins and proetin complexes in excess of 100 kDa. Structures that have been solved this year include the 128 kDa enzyme I and its 146 kDa complex with HPr from the bacterial phosphotransferase system (PTS), and the complex of IIAchitobiose with IIBchitobiose, also from the PTS. 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) and novel relaxation methods. Using these approaches we have been able to characterize sliding and hopping of a multidomain transcription factor on NDA, to characteristics the mechanistic details involving encounter complex formation in protein-protein interactions, and to study the exchange between monomeric and protofibril forms of amyloid Abeta.

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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
Schmidt, Thomas; Ghirlando, Rodolfo; Baber, James et al. (2016) Quantitative Resolution of Monomer-Dimer Populations by Inversion Modulated DEER EPR Spectroscopy. Chemphyschem 17:2987-2991
Bermejo, Guillermo A; Clore, G Marius; Schwieters, Charles D (2016) Improving NMR Structures of RNA. Structure 24:806-815
Deshmukh, Lalit; Schwieters, Charles D; Grishaev, Alexander et al. (2016) Quantitative Characterization of Configurational Space Sampled by HIV-1 Nucleocapsid Using Solution NMR, X-ray Scattering and Protein Engineering. Chemphyschem 17:1548-52
Ceccon, Alberto; Tugarinov, Vitali; Bax, Ad et al. (2016) Global Dynamics and Exchange Kinetics of a Protein on the Surface of Nanoparticles Revealed by Relaxation-Based Solution NMR Spectroscopy. J Am Chem Soc 138:5789-92
Deshmukh, Lalit; Louis, John M; Ghirlando, Rodolfo et al. (2016) Transient HIV-1 Gag-protease interactions revealed by paramagnetic NMR suggest origins of compensatory drug resistance mutations. Proc Natl Acad Sci U S A 113:12456-12461
Cai, Mengli; Huang, Ying; Yang, Renbin et al. (2016) A simple and robust protocol for high-yield expression of perdeuterated proteins in Escherichia coli grown in shaker flasks. J Biomol NMR :
Venditti, Vincenzo; Egner, Timothy K; Clore, G Marius (2016) Hybrid Approaches to Structural Characterization of Conformational Ensembles of Complex Macromolecular Systems Combining NMR Residual Dipolar Couplings and Solution X-ray Scattering. Chem Rev 116:6305-22

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