Protein Crystallography and Structure Determination
Protein Crystallography and Structure Determinationpepperstreet2020-03-26T12:33:05+00:00
Our service isn’t just a final set of co-ordinates, but a detailed analysis of the 3D structure along with our learning and conclusions, driving ideas for project progression and drug design.
Projects are normally broken down into defined stages or milestones based around protein production, initial crystallisation and optimisation and structure determination. Progression to each milestone is dependent on successful delivery of the previous step.
Design of the optimal construct and the ability to screen many different constructs and crystallisation conditions is key to project success.
Purified proteins enter our crystallisation screening process using both commercial and in-house designed sparse matrix crystallisation screens along side any relevant screens based on literature precedent. Tool compounds are used to explore options for co-crystallisation if required.
Improvements to crystal size and quality are developed further and based on our extensive experience in X-ray structure determination of many different protein classes, including kinases, phosphatases, proteases, receptors and Fab-antigen complexes.
X-ray data collection takes place at state-of-the-art synchrotron facilities; we have regular access at number of synchrotrons in UK and Europe, using specialist beam lines when appropriate. The output from data collection is progressed to structure solution via molecular replacement or de-novo phasing by Se-Met or SAD/MAD. Multiple rounds of structure refinement follow, using the industry standard CCP4 software package together with modelling and visualisation software such as Coot and PyMOL.