Structural Biology

The NUVISAN structural biology team, with more than 20 years of experience supporting industrial drug discovery programs, identifies and implements the optimal strategy to deliver timely and high-quality 3D-structural data using macromolecular crystallagrophy, cryo-EM, and NMR techniques. Our state-of-the-art platform allows us to enable structure-based discovery for your targets of interest. We work closely with computational and medicinal chemistry design teams to maximize learning from the structural data and to guide the rational design of improved chemical matter.

Tailored Structural Biology Services Enable Structure-Based Drug Discovery

Our team has extensive experience in enabling the entire gene-to-structure process for a broad range of targets. This allows us to offer a full spectrum of solution-oriented structural biology services to support your project requirements:

  • Strong focus on delivering high-quality and robust platforms with rapid cycle times to efficiently support industrial structure-based drug discovery programs
  • Extensive experience working with a broad range of target classes, including single- and multi-domain soluble proteins, membrane proteins, multi-sub-unit protein–protein and protein–nucleic acid complexes, as well as biologic antibody–antigen targets
  • Expert analysis of target druggability to guide the design of optimal lead-finding strategies
  • We support hit-to-lead and lead-optimization programs with our experience and expertise in 3D-structure interpretation. We offer in-depth binding mode analysis to support and accelerate structure-based compound optimization, enabling full integration of structural learnings into your optimization programs

Our services include:

Protein production for structural biology: Expert designed constructs are expressed and purified by our on-site protein science team to deliver high-quality soluble and membrane proteins suitable for structural biology experiments. Discover more: Protein sciences

Macromolecular crystallagrophy: Structure determination of your target protein in complex with your compounds of interest, achieved through a variety of approaches, including de novo structure determination, optimization of literature targets for industrial crystallography, and our own proprietary Xrays2Go portfolio. Discover more about our crystallography workbench and our Xrays2Go targets

Cryo-electron microscopy: Highly complementary to our X-ray platform, our cryo-electron microscopy structure-determination services deliver structural information for your challenging targets in complex with your compounds of interest. Our in-house sample preparation workbench interfaces seamlessly with regular access to state-of-the-art microscopes at our partner institutes. Discover more: Cryo-EM

Fragment screening: Using our in-house high-throughput crystallography (HTX) platform, we offer crystallographic fragment screening to identify starting points for further optimization campaigns. We can screen different libraries, including the NUVISAN proprietary fragment library and your own in-house fragment collections. Discover more: Fragment screening

NMR: We apply protein- and ligand-observed NMR methods to validate target engagement and characterize your chemical matter, thereby building confidence and guiding your drug-discovery project. In addition, we can also support you with NMR-based fragment screening, from the identification of initial fragment hits through confirmation and analog studies. Discover more about our NMR capabilities and our fragment-screening platform

Small-molecule X-ray crystallography: We also offer crystal structure analysis of small-molecule organic compounds. We crystallize your sample of interest using a panel of different organic solvents, collect diffraction datasets from single crystals using our in-house X-ray equipment, and determine the structure of your compound, including absolute stereochemistry.

Below are some recent highlights of publications from our structural biology team:

X-ray support of small-molecule and biological lead-optimization programs:

Hillig, RC., et al., Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction. PNAS (2019)

Schaefer, M., et al., Allosteric Inhibition as a New Mode of Action for BAY 1213790, a Neutralizing Antibody Targeting the Activated Form of Coagulation Factor XI. JMB (2019)

Rational optimization of unwanted PXR-induced CYP activity: We can help you optimize unwanted PXR activity with our well-established biophysical and X-ray PXR workflow. Read more:

Werner, S., et al., Discovery and Characterization of the Potent and Selective P2X4 Inhibitor N-[4-(3-Chlorophenoxy)-3-sulfamoylphenyl]-2-phenylacetamide (BAY-1797) and Structure-Guided Amelioration of Its CYP3A4 Induction Profile. J Med Chem (2019)