Comprehensive Target Structure Determination Services by Creative Biostructure, Slides of Biology

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Target Single-particle Analysis

Obtaining the accurate three-dimensional (3D) structure information of the target is

helpful for the discovery and optimization of drug candidates, as well as the

mechanism of action (MOA) studies. As a leading service provider in the field of

structural biology, relying on the first-class structural biology technology platformthat

covers X-ray crystallography, cryo-electron microscopy (Cryo-EM) technology and

protein NMR spectroscopy, Creative Biostructure provides a comprehensive solution of

target structure determination, called MagHelix™ Gene-to-Protein and Gene-to-

Structure, complemented with the most advanced biophysical methods to characterize

target and target-ligand interaction. Our services support structure-guided

lead discovery and optimization, as well as biological drug discovery, such as

therapeutic antibody discovery.

2. Target protein expression and purification The service includes recombinant protein expression testing, optimization of protein expression and purification, as well as large-scale protein overexpression and chromatographic purification. Creative Biostructure provides customers with high- performance protein expression systems including E. coli , yeast, insect cells, and mammalian cells. We purify the target protein using the AKTA FPLC systems with multiple chromatographic methods (our standard protocol includes affinity chromatography, ion-exchange chromatography, and size-exclusion chromatography). After purification, the protein can be tested with UV spectrophotometry, SDS-PAGE, and western blot to ensure > 95% purity. The service is available as a stand-alone one or in combination with downstream applications. It is worth mentioning that we support custom membrane protein production.

X-ray Crystallography X-ray crystallography has always been one of the mainstream techniques to solve the high-resolution structure of drug targets. In addition, it provides reliable structural information on target-ligand interaction sites and binding patterns during the screening of hits and optimization of lead compounds. Crystallographers from Creative Biostructure can solve the crystal structure of individual proteins, protein- ligand complexes, and biological complexes. Our crystallography science team expertise includes detailed target know-how, especially in membrane proteins, kinases, phosphatases, and epigenetic proteins.

2. Crystal structure determination X-ray diffraction data is collected on synchrotron beamlines to ensure the highest resolution for your project (providing in-house Rigaku X-ray equipment if necessary). Our data collection specialists can improve the diffraction quality by using cryoprotectants, annealing agents, and dehydrants. After collecting the X-ray data, our scientists find out the initial phases by using the molecular replacement (MR) or single-wavelength anomalous dispersion (SAD) and multi- wavelength anomalous dispersion (MAD) methods. And then, we will build the structural model and refine it. The quality of the final model will be validated through programs such as PROCHECK. Upon request, we can also assist customers in the detailed analysis of the individual protein structure or co-crystal structure to facilitate structure-based drug design. We can prepare crystal-grade protein samples from scratch or obtain them from customers. Moreover, Creative Biostructure also owns the off-the-shelf crystal structure service if customers need it. In-house developed high-purity proteins and crystal structures are readily available for compound soaking and co-crystallization.

Thank you!

Excerpt from: https://drug-discovery.creative-biostructure.com/maghelix- gene-to-protein-and-gene-to-structure-p