It’s important to lay strong foundations for successful drug discovery at this first stage of the process. Our integrated target identification and validation platform combines AI with expert insights, and rigorous lab validation to guide targets through robust evaluation, ready for hit discovery.
Validated, high-quality hits, delivered through integrated technologies and expert collaboration, give you a confident starting point for faster drug discovery.
Turning promising leads into clinical candidates with speed, precision, and the scientific expertise to generate high-quality data and deliver real patient impact.
Delivering integrated, modality-agnostic drug discovery to tackle complex biology, accelerate development, and advance innovative therapies with confidence.
Advancing next-generation ADCs through payload-focused design, integrated expertise, and collaborative innovation to deliver safer, more selective therapies.
Driving biologics innovation through integrated design, structural biology, and multidisciplinary expertise to accelerate next-generation therapies from concept to clinic.
Combining deep therapeutic expertise with translational insight to design strategies, reduce risk, and accelerate discovery programs toward clinical success.
Accelerating oncology drug discovery through integrated expertise, innovative modalities, and translational insight to deliver candidates with real clinical impact.
Driving immunology and inflammation drug discovery through tailored assays, translational models, and integrated expertise for faster clinical success.
Advancing CNS drug discovery through integrated models, translational biomarkers, and multidisciplinary expertise to overcome complexity and accelerate therapeutic innovation.
Designing and advancing differentiated small-molecule therapies for obesity and diabetes through integrated expertise, mechanistic insight, and translational strategies.
Inobrodib, an exciting, first-in-class oral anti-cancer drug in clinical development by CellCentric, was collaboratively designed, synthesised and supported on its pre-clinical journey by an integrated project team at Sygnature Discovery. Inobrodib is now showing promising results in Phase I and II trials for multiple myeloma and other cancer types.
It’s important to lay strong foundations for successful drug discovery at this first stage of the process. Our integrated target identification and validation platform combines AI with expert insights, and rigorous lab validation to guide targets through robust evaluation, ready for hit discovery.
Validated, high-quality hits, delivered through integrated technologies and expert collaboration, give you a confident starting point for faster drug discovery.
Turning promising leads into clinical candidates with speed, precision, and the scientific expertise to generate high-quality data and deliver real patient impact.
Delivering integrated, modality-agnostic drug discovery to tackle complex biology, accelerate development, and advance innovative therapies with confidence.
Advancing next-generation ADCs through payload-focused design, integrated expertise, and collaborative innovation to deliver safer, more selective therapies.
Driving biologics innovation through integrated design, structural biology, and multidisciplinary expertise to accelerate next-generation therapies from concept to clinic.
Combining deep therapeutic expertise with translational insight to design strategies, reduce risk, and accelerate discovery programs toward clinical success.
Accelerating oncology drug discovery through integrated expertise, innovative modalities, and translational insight to deliver candidates with real clinical impact.
Driving immunology and inflammation drug discovery through tailored assays, translational models, and integrated expertise for faster clinical success.
Advancing CNS drug discovery through integrated models, translational biomarkers, and multidisciplinary expertise to overcome complexity and accelerate therapeutic innovation.
Designing and advancing differentiated small-molecule therapies for obesity and diabetes through integrated expertise, mechanistic insight, and translational strategies.
Inobrodib, an exciting, first-in-class oral anti-cancer drug in clinical development by CellCentric, was collaboratively designed, synthesised and supported on its pre-clinical journey by an integrated project team at Sygnature Discovery. Inobrodib is now showing promising results in Phase I and II trials for multiple myeloma and other cancer types.
scientific solutions | protein science & Structural Biology
Single Particle Cryo-EM
Sygnature Discovery delivers a complete gene-to-structure pipeline for even the most challenging targets. Our integrated cryo-EM capabilities combine advanced technology and proven expertise to help you visualize complex macromolecules with precision and speed.
Single particle cryo-electron microscopy (cryo-EM) is a powerful technique for high-resolution visualization of biological macromolecules. It offers unique advantages for studying large dynamic complexes, flexible proteins, and membrane proteins, targets often less amenable to alternative structural methods such as X-ray crystallography or NMR.
At Sygnature Discovery, we harness the power of cryo-EM to determine macromolecular structures and conformational states that are otherwise difficult to capture. Our team has a proven track record in delivering high-quality, difficult-to-produce protein targets, ensuring optimal sample preparation for structural studies.
Protein Quality Assessment
Protein quality is critical for a successful cryo-EM project. We use a suite of analytical tools to validate samples before grid preparation, including:
• Analytical size-exclusion chromatography (SEC)
• Tandem mass spectrometry (MS-MS)
• Flow-Induced Dispersion Analysis (FIDA)
• Negative stain electron microscopy
Grid Preparation & Data Collection
We prepare grids using an in-house Vitrobot IV, the industry standard for cryo-EM.
Through partnership with leading facilities-including LonCEM, eBIC (Diamond Light Source), and the Universities of Manchester, Leicester, and Leeds – we provide access to state-of-the-art microscopes, such as Titan Krios. Our scientists handle gird screening and data collection to deliver high-quality datasets tailored to your project.
Data Processing & Infrastructure
Our in-house data processing is powered by secure, scalable cloud computing through Amazon Web Services (AWS). This infrastructure enables rapid, on demand analysis without delays or resource bottlenecks, ensuring your project moves forward efficiently.
Project Management & Risk Mitigation
Cryo-EM projects often require iterative optimization. Our workflow inc ludes strategic stop/go decision points to manage risk and maximize efficiency. We maintain regular, transparent communication throughout the project, providing an honest assessment of progress, next steps, and cost guidance.
Cryo-EM Process Overview
Our streamlined gene-to-structure approach eliminates delays and preserves sample integrity:
Construct Design
Based upon literature review, modelling and any prior experience, including accessory proteins if needed.
Small Scale Feasibility Studies
Expression and purification experiments to identify the optimal host/construct combination, supported by rigorous QC analysis.
Scale Up
Production the target protein(s), in sufficient quality and quantity for grid preparation, with QC tests such as SEC, SDS-PAGE, FIDA, mass spectrometry, and negative stain EM.
Grid Preparation and Screening
In-house grid preparation and screening with test datasets for 2D and 3D classification.
Full Data Collection
Access to Titan Krios microscopes with our scientists conducting experiments.
Data Processing and Modelling
Rapid, secure processing via Amazon Web Services (AWS) cloud software – no queuing required.
Hear From One of our Experts
“We can support all stages of a single particle cryo-EM project from construct design through to refined structure. Protein quality is the key factor for structure determination by cryo-EM and often the most interesting targets are the toughest to produce. We have extensive experience in producing difficult proteins, including membrane proteins.”
Valerie Pye
Associate Director of Protein Science and Structural Biology
Importance of metabolic GPCRs Metabolic GPCRs play a vital role in how our bodies manage…
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Related Solutions
We bring together a dynamic blend of new talent and experienced pharmaceutical industry experts from a round the world, delivering excellence across every stage of discovery.
Main home page for the Protein Science and Structural Biology Department. We take time to understand your target and the ultimate aims of the project and tailor our approach accordingly.
This complex and diverse class of proteins are amongst the most valuable for drug discovery. At Sygnature we have a team of specialists dedicated to the production of these challenging targets.
We provide various NMR services, including protein characterization and ligand binding in solution, fragment-based drug discovery and gene to NMR structure determination.
We not only provide a full gene to X-ray crystallography structure service but support your project with our insight and expertise, with a milestone-based approach.
