Macromolecular Crystallography – NUVISAN

We help you to accelerate your hit-to-lead and lead-optimization campaigns by elucidating the 3D molecular binding modes of small-molecule modulators or therapeutic proteins (biologics) bound to their target proteins. This 3D information provides an experimental understanding of ligand binding to enable structure-based drug design. Our protein crystallography platform allows us to develop high-quality crystallization systems that deliver timely structural information to support your optimization programs.

Construct Design and Selection

The design of suitable constructs is key for a successful structure determination for your target protein. Based on target experience, bioinformatic analyses, and limited proteolytic digest analyses, we identify a set of different-length construct variants suitable for addressing the aims of your program. Our protein science labs perform expression and purification tests to identify the optimal conditions for target protein production. Biophysical methods (including TSA and nanoDSF) may be used to identify optimal constructs, buffer composition, or early hit list compounds that stabilize the target protein and facilitate crystallization.

Crystallization Screening

Our state-of-the-art crystallization platform, which enables fast and efficient screening to identify and optimize crystallization conditions, includes:

  • crystallization screen preparation using Freedom EVO (Tecan) and FORMULATOR (FORMULATRIX) liquid-handling systems
  • broad panel of proprietary and vendor screens, including protein-class-specific sparse-matrix crystallization screens (e.g., antibody screens)
  • accurate drop setting using Mosquito nanoliter liquid-handling machines (including humidity control box)
  • specialized membrane protein liquid cubic phase (LCP) crystallization platform, including an LCP mixing station and an LCP-enabled Mosquito nano-dispensing robot
  • specialized fragment-screening platform, including an Echo Acoustic Liquid Handler for soaking experiments and a Crystal Shifter for crystal freezing
  • automated crystallization imaging (visible and UV) at 4°C and 20°C using the FORMULATRIX ROCK MAKER imaging systems

Data Collection, Structure Determination, and Analysis

Regular bi-weekly access to third-generation high-brilliance synchrotron sources is complemented with our in-house automated crystal screening sample changer and two X-ray sources. Together, they support rapid and regular data collection. Our in-house X-ray platform includes:

  • Rigaku MicroMax rotating anode generator (007HF) equipped with a PILATUS 200 detector and ACTOR robot for automated sample mounting
  • Rigaku XtaLAB Synergy-S generator equipped with a HyPix-6000HE detector

Supported by our proprietary automated structure-solution pipeline, datasets are evaluated and structures are fully refined. Following a final internal quality control check, we deliver a structural biology data package containing a full set of industry-standard files.

Together with our DLS team, we complete the structure-determination activities by offering an in-depth binding mode analysis to support and accelerate structure-based compound optimization and to help enable full integration of structural learnings into your optimization programs.


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