Structure Determination

Best-in-class targets for protein crystallization and structural determination 

Our high-quality membrane protein crystallization and native target stabilization services tailored to (bio)drug discovery for Pharmaceutical and biotechnology companies, as well as academic teams in the life sciences.

Our membrane protein structural determination approach offers the access to high-quality and reliable targets or native & functional antigens, suitable for various applications. This enables the discovery of primary leads through Structure-Based Drug Design (X-ray and cryo-EM) with full-length and functional membrane proteins, offering distinctive advantages.

Eurofins CALIXAR’s structural biology services are ideal for:

• Drug discovery stages (Screening by SBDD or FBDD; Drug Design before hit and lead validation).
• Preclinical stages (toxicity and mechanism of action studies).

Eurofins CALIXAR’s structural biology membrane protein crystallization services particularly for native and functional membrane proteins to render:

• X-ray crystallography structures using vapor diffusion or Lipidic Cubic Phase (LCP)
• 3D Structures determination Cryo-EM in collaboration with world leading experts (PR IGBMC)
• NMR studies or protein/ligands interaction (Igonet S. et al., Scientific Reports)

High resolution for protein structural research

Cryo-Electron Microscopy (Cryo-EM)

Cryo-Electron Microscopy (Cryo-EM) is a powerful imaging technique used in structural biology to study the detailed structures of biological macromolecules, such as proteins and nucleic acids. Unlike traditional electron microscopy, which requires samples to be dehydrated and stained, Cryo-EM involves freezing samples in a thin layer of vitreous ice. This process preserves the native structure of biological molecules, allowing researchers to observe them in their near-native state.

Cryo-EM revolutionizes protein structure determination by preserving the native state of biological macromolecules. Unlike traditional methods, Cryo-EM employs flash-freezing techniques to capture specimens in a thin layer of vitreous ice, avoiding the need for dehydration or staining. This preservation of native conformation enables researchers to visualize proteins in their physiologically relevant state. The technique's high-resolution capabilities, facilitated by advanced detectors and sophisticated image processing algorithms, allow for the determination of protein structures with remarkable detail. Flexibility in sample preparation and the ability to study challenging targets, such as membrane proteins, further underscore Cryo-EM's significance in elucidating intricate molecular architectures. In the realm of structural biology, Cryo-EM stands as a transformative tool, providing unparalleled insights into the structure and function of diverse biological macromolecules.

X-ray crystallography

X-ray crystallography is a powerful technique employed in structural biology for determining the three-dimensional structure of proteins and other biological macromolecules. In X-ray crystallography, the protein of interest is crystallized, and a beam of X-rays is directed through the crystal. The X-rays interact with the electrons in the crystal, producing a diffraction pattern. By analyzing this diffraction pattern, scientists can deduce the electron density of the crystal, revealing the atomic structure of the protein.

Two common methods within X-ray crystallography are vapor diffusion and Lipidic Cubic Phase (LCP):

1. Vapor diffusion: In vapor diffusion, a protein solution is mixed with a precipitant solution, and the resulting mixture is allowed to equilibrate against a reservoir solution containing a higher concentration of the precipitant. As the solvent evaporates, crystals of the macromolecule form. These crystals are then exposed to X-rays, and the resulting diffraction pattern is used to determine the arrangement of atoms within the crystal lattice. Vapor diffusion is a widely used technique due to its versatility and suitability for a range of macromolecules.
2. Lipidic Cubic Phase (LCP): LCP is a specialized method used primarily for the crystallization of membrane proteins. It involves embedding the membrane protein in a lipidic mesophase—a gel-like, crystalline material. The protein-laden mesophase is then dispensed onto glass plates and covered with a second glass plate to create a sandwich-like structure. Crystals form within this lipidic environment. LCP is advantageous for membrane proteins because it mimics the natural lipid bilayer environment of these proteins. This method has been particularly successful in obtaining high-quality crystals for challenging membrane protein targets.

Protein crystallization - structural biology studies and 3D structure determination

Obtain access to the best stabilized native, wild-type, unmutated, untruncated and crystal-grade targets, facilitating structure investigation of membrane proteins, both in isolation and in complex with small molecule compounds or antibody fragments.

Save time and money by employing CALIXAR as your unique membrane protein crystallization service provider for all assays all in one place. Obtain precise understandings of sample requirements (quantity and quality) for structural biology applications.

We can maintain protein-protein interactions in native environments, enabling us to generate highly relevant and reliable information about membrane proteins for our clients.

Access to CALIXAR's membrane protein structural determination technology

Each of our clients obtain access to our exclusive technology and know-how (8 patent families, more than 28 publications).

The CALIXAR® platform utilizes patented technologies only open for clients under specific contracts (license, co-development, and services).

You can leverage CALIXAR’s proprietary technology as well as additional best-in-class membrane protein technology that are unobtainable in the market.