Advantages Disadvantages Non-destructive technique Proteins in the range of 5-25 kDa require uniform labelling with 15N and 13C isotopes. Sometimes, partial deuteration is needed Macromolecular structure can be determined in solution, under wide range of ionic strength, pH (

Advantages Disadvantages Amenable to large macromolecular complexes Viewing smaller proteins (

scientific solutions | Protein Science & Structural Biology

Structural Biology

At Sygnature Discovery, we help you gain the structural insights that drive smarter drug design. Our scientists combine advanced techniques with deep expertise to reveal how proteins and nucleic acids behave at the molecular level, turning complex data into actionable strategies for your program.

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3D molecular structure and ribbon diagram illustrating protein science and structural biology techniques such as cryo-EM, X-ray crystallography, and NMR spectroscopy.

supporting your research

We select the right structural approach for your specific target-whether it’s a protein or nucleic acid- and align it with your project goals.

This could include confirming compound binding, guiding structure-based drug design, mapping epitopes, running fragment screens, or supporting other applications.

Our solutions go beyond delivering a set of coordinates. We provide comprehensive 3D structural analysis, share insights gained during the process, and deliver conclusions that shape project direction and inform drug design strategies.

D structural models of biomolecules, representing structural biology techniques for drug design, epitope mapping, and fragment screening

Our Structural
Biology Solutions

Protein quality matters. The
success of any structural biology
study depends on the quality of
the protein. We dedicate time to
careful planning and apply our
expertise to ensure the protein is
of the highest standard,
significantly increasing the
likelihood of a success.

Structural biology projects are
often best tackled with an iterative
approach. We follow a milestone-
based process where data is
reviewed at key points and next
steps agreed collaboratively. This
keeps us guided by the data,
reduces risk, and ensures the
most efficient path forward.

Our Capabilities

Which Structural Biology
Technique Should I Choose?

Choosing the right technique depends on your target and project objectives. We’ll advise you on the most suitable option. Below is a summary of the advantages and disadvantages of each method. For an in-depth description and comparison of the techniques we offer read more in our blog here.

Advantages	Disadvantages
Well established techniques	Requires sample to crystallise
Can achieve atomic resolution of macromolecular structure in crystalline state	Crystals need to be well ordered to achieve a high resolution diffraction
High throughput once crystal system established	Snapshot of conformation
No size limitation of macromolecule	Radiation damage – this can be mitigated to some degree
Data collection, processing, and analysis is relatively quick	Crystal packing can influence conformation
	Requirement to solve phase of diffraction data to calculate electron density
	X-ray source (in-house or synchrotron) required with appropriate goniometer, detector, etc needed for data collection

Advantages	Disadvantages
Non-destructive technique	Proteins in the range of 5-25 kDa require uniform labelling with 15N and 13C isotopes. Sometimes, partial deuteration is needed
Macromolecular structure can be determined in solution, under wide range of ionic strength, pH (<7.4) and temperature conditions	Isotopes required for protein labelling are expensive and the cost increases as follow per L of media: 15N(£)<13C(£x8)
Peptides with a maximal range of 3-4 kDa do not require isotope enrichment	High concentrations of sample is required (~1mM). Unable to assign N and C atoms
NMR in solution can explore a wide range of macromolecular properties and not restricted to structure determination: Dynamics Folding Interactions Kinetic reactions in real time	De-novo protein synthesis is the only available method to incorporate isotopes into proteins and this is predominantly restricted to either E.coli or cell-free expression systems
	High protein concentration is required, and it needs to be stable in solution for a period of minutes to hours.
	Oligomeric and/or heterogenic samples are challenging
	Data acquisition, processing and analysis is relatively slow
	An NMR spectrometer (above 500MHz), equipped with a cryoprobe is required for data collection

Advantages	Disadvantages
Amenable to large macromolecular complexes	Viewing smaller proteins (<150 kDa) is challenging, size can be augmented with additional binding partners
Can achieve near atomic resolution of proteins in their native (frozen hydrated) state	Data acquisition, processing, and analysis is relatively slow
Multiple states of a macromolecule can be purified in silico from a single data set	Computationally expensive (data storage and GPU)
Macromolecules viewed in real space, no phase problem	Radiation damage – this can be mitigated to some degree
	200kV or 300kV electron microscope required for data collection