Automated NMR for Protein Assignment and Structure Determination in a Timely and Affordable Way

NMR is a very versatile tool in structural biology, offering new capabilities in protein structure resolution. With (ultra)-high field instruments and AI-based software solutions, it's now more applicable and efficient, enabling precise identification of binding molecules and interaction characterization, thus revitalizing its importance in early drug discovery programs, amongst other applications.

As part of a fragment-based drug discovery program, we demonstrate how we solved a 20-kDa cancer related protein structure in a timeframe competitive with X-ray crystallography or cryo-EM. The atomic resolution structure obtained together with 15N-1H-HSQC CSP reveals very clear to derive binding poses of millimolar affinity fragment identified during LO-NMR screening campaigns. A complex protein/ligand structure from the NovAFraG library is exemplified. The minimal NMR dataset necessary to get assignments and calculate structures is deeply investigated throughout this real-case study, in a constant search for optimized workflows. We are also going to give an outlook of other applications enabled by easy access to protein assignments.

At the end of the seminar, you will have an understanding of what you can get from the AI-based NMRtist platform and an optimized NMR data acquisition scheme. You will also get a detailed view on how the results obtained can be used for further analysis such as ligand interactions studies.

Key Learning Topics

• Rapid automated NMR protein structure determination
   
• (Ultra)-High field NMR
   
• NMR for low affinity fragment binding poses

Presenter: Dr. Marc Vitorino (Head of NMR, NovAliX, Strasbourg, France)

I am a structural biologist by training who chose early in his career to join the industry and the field of early drug discovery.

After completing my Ph.D. in France, I moved to Cambridge as a research associate in the biophysics group of Dr. Glyn Williams at Astex Therapeutics, where I specialized in applying the technique of liquid-state NMR spectroscopy to identify new fragments, that could potentially lead to new approved drugs on the market.  

At NovAliX, as head of the NMR platform within the biophysics group of Dr. Renaud Morales, I am mainly interested in applying the technique of liquid-state NMR spectroscopy with fragment libraries to study different therapeutical target proteins, identify new binding molecules and characterise the interaction between the fragment and the protein of interest. To help our customers initiate their early drug discovery programs, I work on developing methods to make the liquid-state NMR technique more applicable.

Presenter: Dr. Daniel Mathieu (Application Scientist, Bruker BioSpin)

Daniel started studying Chemistry at the Goethe University in Frankfurt in 2001.

In 2007 he got his diploma in Chemistry. He then joined the group of Professor Harald Schwalbe at the University of Frankfurt for his PhD thesis developing NMR methodology for RNA and peptides, which he finished in 2011.

Since 2011 he’s an application scientist at Bruker BioSpin in Germany, focusing on Biomolecular NMR.