NMR Seminar: POKY, The Software Suite for NMR Studies and More

MS Teams

Abstract NMR spectroscopy is a powerful technique for molecular studies. In biomolecular research, it offers a wide range of unique approaches, from analyzing small compounds to investigating macromolecules, and from examining purified samples to studying complex mixtures. NMR analysis is primarily conducted in dry laboratory settings. Once the sample is prepared and inserted into the spectrometer, nearly all processes are performed using computers. When it comes to spectral analysis of biomacromolecules, such as proteins and nucleic acids, Sparky has been the gold standard program for a few decades. Donald Kneller from the Tack Kuntz group and Tom Goddard from the Tom Ferrin group were early contributors to UCSF-Sparky in the 90s. I took over from the University of California, San Francisco (UCSF) and developed NMRFAM-Sparky at the National Magnetic Resonance Facility at Madison (NMRFAM) until 2020 before I moved to the University of Colorado Denver. Since then, my group has developed the new program, POKY. POKY succeeds all the previous capabilities while provides new and enhanced features, leveraging the recent AI revolution. It is highly automated and efficient, covering assignment, peak picking, relaxation, dynamics, metabolomics, and small compound analysis. Additionally, POKY incorporates self-teaching capabilities. We have identified six different challenges,

NMR Seminar: Structural Determination of Neurodegenerative Disease-Associated Proteins Inside Cells

MS Teams

 Abstract The misfolded proteins associated with neurodegenerative disease can adopt a variety of different conformations, some of which are toxic. Because these proteins have identical amino acid sequences, the cellular environment clearly influences the final state, yet most structural studies do not include the cellular context and, perhaps because we are not studying the correct conformation, not a single therapeutic strategy for these diseases addresses the underlying protein misfolding pathology. Using new sensitivity-enhancement technology for solid state NMR spectroscopy, Dynamic Nuclear Polarization, we study protein structure in native environments -inside living cells -to reveal how both healthy and disease-relevant cellular environments influence protein structure. Because NMR reports quantitatively, with atomic level precision, on all sampled conformation, it can not only report on structural polymorphs but also provide experimental restraints on regions of intrinsic disorder, complementing insights from cryo-electron microscopy and tomography.Using this approach, we recently demonstrated that an amyloid fibril with a solved cryo-EM structure was polymorphic and found that when those fibrils were used to seed amyloid propagation in mammalian cells, the minority polymorph in the purified setting became the majority polymorph inside cells. With this approach we can understand the mechanism of protein-based inheritance of amyloid aggregates and

NMR Seminar with Rongfeng Zheng

MS Teams

Title: Chalcogenide-Stabilized Metal Nanoclusters: Synthesis, Characterizations, and Applications Abstract: This seminar focuses on the atomically precise gold NPs, or NCs. Au25(SR)18 was selected as a model NC to investigate their magnetic properties, with pentanethiol, hexanethiol and octanethiol used as bonding ligands. Both negatively charged and neutral NCs were synthesized, and 1H/13C NMR were used for detailed structural analysis, as well as surface bonding ligand environment analyses. The anion NC (diamagnetic) and neutral (paramagnetic) NCs are compared and by using the diamagnetic chemical shifts as references, paramagnetic Knight shifts can be calculated. These shifts measure the spin density along the carbon chain of the surface ligand. Temperature dependent NMR was used to study the spin density effect. Density functional theory calculations were used to predict the spin density on Au25(SC8H17)18 and compared with the Knight shifts observed from the experiments. New magnetic properties were observed from the Knight shifts plots. Chalcogenide stabilized NCs, such as with selenolates and tellurolates, have been less investigated, especially their exchange reactions with thiolate. The reaction mechanism, specifically the site preferences and how the mixed ligand layer is distributed on the NCs surface in the exchange reaction, is much less understood. PhSeH and (PhTe)2 were used

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