NMR Console Avance NEO 800 MHZ

About This Grant

Abstract In an era where static structural information about biomolecules is readily available from de novo structure prediction programs, understanding dynamics, allostery, conformational changes, and the effects of disease- causing mutations is critical for mechanistic studies. Solution NMR uniquely provides this vital information and plays a unique role in addressing disordered regions of the human proteome and elucidating their functional roles. Consequently, there has been increased interest in using NMR to paint a more complete molecular picture. For decades Harvard Medical School have been pioneering new NMR methods and applying them to challenging systems. However, the recent ending of the NIH program project grant that supported the MIT magnet lab and the quench of the 900 MHz magnet at MIT have left a significant void in high-field instruments in the Boston area. The current flagship high-field spectrometer, the 800 MHz at DFCI, has a 19-year-old console, the brains of the instrument, which is outdated and incompatible with new operating systems and software. In terms of functionality the spectrometer is essentially stuck in the year 2018. Upgrading to a new console will equip the Arthanari lab with the capabilities to deploy their new NMR methods and make their existing methods operate more efficiently. The new method such as in situ/Closed-loop optimization of NMR pulse sequences and Stochastic NMR which require the capabilities of a new console. The Arthanari lab has developed nitrogen detection methods with TROSY selection which holds potential to unlock new frontiers in NMR studies, especially for challenging proteins, such as disordered proteins and proteins that can only be expressed in eukaryotic systems, where traditional NMR fails. This 800 MHz also has a TXO probe which is tailored for maximum sensitivity for 15N-direct detection. This spectrometer at DFCI is used by several NIH-funded groups in the area, including Harvard, MIT, Boston University, and Boston College, as well as researchers from across the globe. The unique combination of expertise in NMR methodology, biochemistry that allows innovative labeling, and innovative data acquisition in the Arthanari lab, along with a track record of maintaining a world-class facility for the last 30 years in the Longwood Medical Area, makes the collaborative work here highly productive, turning challenges into opportunities for innovation. This facility benefits from the wisdom of experienced scientists and core directors, as well as the fearless pursuit of ideas by young researchers. The NMR methods developed here present an opportunity to democratize NMR by enabling automation in both setting up experiments and analyzing data, thereby opening the use of NMR to non-experts. This new console will usher in a new era for NMR at the Longwood Medical Area, rejuvenating scientific quests and development of new NMR methods. The well-oiled and time-tested NMR infrastructure here will ensure easy access, efficient workflow, adequate training, proper maintenance, and access to robust and cutting-edge methods, leaving no stone unturned.