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  1. Capabilities
  2. X-Ray Crystallography

X-Ray Crystallography

3D structure determination is an integral part of drug discovery and development. Our in-house generated protein structures and analysis are used to identify hits, develop early leads, and optimize pre-clinical compounds. High-resolution crystal structures of target proteins provide atomic details that empower chemists to optimize leads quickly and with confidence. 


Our structural biologists have been focused on novel protein targets, aiming to provide invaluable structural information and detailed insight into drug discovery programs. 


Structure-based drug design (SBDD) is increasingly regarded as a vital component of drug discovery projects. It can be used to optimize lead compound specificity and binding affinity, while enhancing efficacy, by eliminating unwanted physiochemical properties to yield more efficient candidates. HitGen has been a long-standing proponent of SBDD, and not surprisingly, we have a strong in-house team of X-ray crystallographers and molecular modelers. By coupling this structural biology know-how to HitGen’s capabilities in SBDD, and fragment-based drug design (FBDD), it enables our medicinal chemistry and computational chemistry teams make use of this information throughout the drug discovery process to optimize ligand design and produce the most effective candidate molecules.


HitGen has the in-house expertise and facilities to undertake high-throughput screening of thousands of crystallization conditions, and through world-class synchrotron facilities, such as the SSRF (Shanghai, China), and the Spring-8 synchrotron radiation facility (Hyogo, Japan).


We generate high-resolution datasets for target proteins (apo or ligand-bound). The structural data is then processed by our experts, and the solved the structures are presented in a variety of formats suitable for computational modelling.

Over the last few years, our Protein Science team has solved over dozens of protein-ligand structures (PLS) involving mainly small molecules from our proprietary DELs.


As proteins are fundamental for Protein X-ray crystallography, HitGen's protein science team offers to design and generate high-quality proteins for advanced research applications.


Single standard crystallographic services can also be provided, including initial crystallization, crystal optimization, data collection, structure solution, generation of movies to show any features of a given structure. 

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General crystallography process at HitGen

Step1: Crystallization screening (for identification of crystallization hits) 

  • Initial screening will be set up to 1000-2000 conditions at different temperatures, using our high throughput nanoliter dispensing robot (Mosquito® LCP), saving time and making efficient use of precious samples. 

  • Automated imaging for crystal evaluation (UVEX-ps256, Jansi)

  • Daily diffraction experiment is performed on in home lab X-ray sources (Bruker D8 VENTURE with METAJET and CPAD


Step2: Crystallization optimization (by multi-dimensions for optimal crystal conditions)

  • Correlation of images & experimental setup (database)

  • Reproduction and multi-dimensional optimization of crystal conditions 

  • Crystals from coarse matrix screens are optimized using fine screens, additives, and seeding.


Step 3: Crystal Structure Determination

  • Co-crystallization with ligands (mainly small molecule compounds from DEL screening or clients’ compounds) or soaking them in the apo protein crystals will be performed prior to data collection;

X-ray data collection is mainly performed on a monthly schedule at the industrial synchrotron beamlines (at SSRF or Spring-8), ensuring the highest resolution for the crystal structure. 


For each protein crystallography project, we accelerate data processing and structure solutions via automated programs, meanwhile, the essential steps, such as Ligand fitting and finalization of the structures, are performed manually by our experienced crystallographers. Crystal structures are solved with molecular replacement or advanced de novo phasing techniques, followed by a detailed comparative analysis of the protein co-crystal structures, with the important interactions and the ligand-induced conformational changes highlighted. 


Our experts verify and interpret every single structure carefully before delivery. All structures delivered passed our quality control criteria, that is, the PDB standard.

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