Structural Biology Services
Sapient Discovery offers structural biology contract and consultant services as a cost-effective and powerful approach to help validate and guide medicinal efforts in the drug design and optimization process. SD’s structural biology facility provides protein production and X-ray crystallography services with end result of providing at atomic level a 3D snapshot of the small molecule with the target protein. The structural details of interactions and conformations of protein target and co-crystal structures of target with customer’s small molecule provides structural insights for exploitation of the target for the design of more select and potent inhibitors that custom-fit into the protein target of interest.
Construct Design: At Sapient Discovery we first use bioinformatic tools to design protein constructs that are suited for the structural studies. Using structural and function information constructs are designed and engineered. N- and or C-terminal peptide/protein tags are engineered to help in the expression and protein purification stages.
Mutations: Amino acid mutations are engineered into the target protein to improve solubility and crystallization or help in further elucidating the structure activity relationship and mode of interaction of the inhibitor.
Selenomethionine Incorporation: Sapient Discovery can generate selenomethionyl derivatives of the target protein in instances where X-ray structure elucidation requires additional electron density improvement or phase determination via multi-wavelength anomalous dispersion (MAD).
Cloning & Expression
A handful of designed protein constructs encompassing the structural domain of interest are cloned and expressed in several systems. Multiple expression systems and conditions are performed in small-scale pilot tests to determine the optimal expression of soluble protein for large-scale protein production.
Proteins are purified to crystallography grade using one or more purification steps.
Protein Production Services
Sapient Discovery’s protein production capabilities could be accessed for producing novel proteins as a fee-for-service. Proteins are routinely expressed and purified in our laboratory in milligram quantities for crystallography studies.
X-ray Crystallography Services
Sapient Discovery offers X-ray crystallography services to accelerate customer’s pre-clinical drug discovery programs providing a powerful tool at both the hit-to-lead and lead optimization stages. We are now seeking companies who might have a need for X-ray crystallographic services to work with us on a fee-for-service mode, to bring protein crystal structures to their drug-discovery/vaccine research/protein engineering efforts.
Sapient Discovery uses its proprietary crystallization screening conditions at both the pilot and scale-up crystallization stages. The small molecule candidate is either co- crystallized with the protein or is soaked into the final protein crystal in a temperature-controlled environment.