CrystalsFirst GmbH products

X-ray crystallography is a strong method for studying biomolecules’ 3D structure. Data gathering technologies for synchrotron radiation have improved, making this approach even more effective and efficient. The crystal is exposed to an intense stream of X-rays for getting high-resolution structural information. The protein crystals deflect these X-rays, resulting in dispersed beams and a diffraction pattern. The intensity and position of spots in the diffraction pattern allow the generation of an electron density map, which enable the identification of each atom in the protein as well as well as in any bound ligands and solvent molecules. Chemical bond lengths and angles may be determined with angstrom precision and a tenths of a degree, respectively, using this data. We can validate the location of a molecule’s contact with a protein, as well as how the chemical and protein are conformationally modified as a result of this interaction, using this information.

Our proprietary technology SmartSoak® enables an up to 10X accelerated process in crystallography by solving the problems of crystal soaking. SmartSoak-enabled crystallographic screens deliver hit rates up to 30 %. It’s application is independent from the modality:  it can be used for non-covalent and covalent compounds. The technology is independent from the nature of the protein and has been successfully applied for over 30 different protein targets.

FragAI is an automated workflow for generation of active molecules for therapeutics development using chemoinformatics, bioinformatics and machine learning. Our methodology uses the data flow from SmartSoak and FastForward output. The step of fragment hit expansion and evolution builds on validated fragment hits. The sampled chemical space can be adapted flexibly. Also, FragAI follows the paradigm of putting “structural data first” to identify bioactive compounds leading to shorter computational time and in parallel to higher success rates.