Structural Biology

15+ scientists with extensive X-ray crystallography, NMR and Cryo-EM  industrial and academic experience. Structures solved of many different protein classes, including membrane proteins, protein complexes and recently RNA.

With capabilities across

X-ray Crystallography

• Crystallisation/co-crystallisation screening of proteins, DNA, and RNA using in-house and commercial screens at various temperature.
• Co-crystallisation and soaking optimization for co-structure determination.
• Nanoliter drop dispenser is used to rapidly screen hundreds of conditions with minimum amount of sample.
• Automated crystal imaging robots with the Formulatrix RockImager at two temperatures for efficient follow-up of crystallization.
• Extensive use of seeding techniques for rapid onset of crystallisation and crystal optimization and diversification of crystal forms through MMS.
• Structures are solved by molecular replacement (MR), single anomalous dispersion (SAD) or multi-wavelength anomalous dispersion (MAD).
• Regular access to 7 synchrotron sources for data collection around the world.

Figure A: Crystal structure of the BabA extracellular domain solved by single-wavelength anomalous diffraction (SAD).

NMR

• Capability to produce 15N, 13C, 2H protein labelled protein in minimal media to support NMR.
• Expert spectroscopists in house and access to several high-end instruments.
• Structure determination of targets alone or in complex with ligand.

Cryo-EM

• Expert microscopists in house and access to high end microscopes for screening and high resolution data collection (Glacios, Tecnai, Titan Krios).
• In-house and Amazon Web Services (AWS) cloud platform for data processing.

Figure B: 5HT2a Cryo-EM structure solved in house from Gene to Structure.

Fragment Based Drug Discovery

• Crystallographic fragment screening using a high solubility curated fragment library devoid of soluble aggregates.
• Curated covalent fragment library also available.
• PANDDA analysis for rapid delivery of a hit list.
• Fragment analogs identified for rapid follow-up.
• Learn more.

Why choose Sygnature for your Structural Biology Project?

High quality protein production in-house

• Protein quality is the key factor for structure projects. Especially cryo-EM targets that are some of the toughest to produce. We have extensive experience in producing difficult proteins, including membrane proteins.
• We have the tools to perform quality checks prior to crystallisation or cryo-EM grid preparation to ensure the best protein is taken forward (e.g., analytical SEC, MS-MS, FIDA, negative stain EM).

Gene to structure pipeline

• We have experts to oversee all steps of the project, delivering a ready to use refined protein model as the end goal. We will assist you to understand the data provided.
• Scalable processing power offered by Amazon Web Services (AWS) cloud platform provides ability to process large data sets rapidly and on-demand. No queuing for computational resource required. Secure Data.

Risk management

• A structure project can be an iterative project where individual stages need further optimisation.
• Our workflow include various key decision points to reduce and manage this risk.
• We regularly meet with clients and will offer honest assessments of project status and advise around cost/risk.

To Learn More

Read our Protein Science and Structural Biology case studies and blog articles here