There are a bunch of people doing this – in the small molecule world. And a lot of work has been done on some very robust protein systems too. Can you guess which ones?
The real issue (at the moment) is that all the pre-work needed to predict if or how a protein might crystallise takes more work and more protein than setting up crystallisation experiments. How many people do DSL on protein in a crystallisation screen, for example? Or do self-association chromatography to determine the B22 (which changes under different conditions, naturally). Or try mapping out a phase diagram (for each condition)? Many people are not even aware that a simple PCT can help one work out a sensible starting concentration for crystallisation trials. As for AI, at the moment unsupervised learning doesn’t seem to do much, which means we need vast, well annotated datasets to make progress. MARKO, which Sarah mentioned, required half a million scored images, which took years to get together. Janet From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> On Behalf Of Keller, Jacob Sent: Wednesday, 24 July 2019 4:18 AM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] challenges in structural biology What about developing a theory of how crystallization happens, i.e., what does the microscopic “picture” look like when crystals are forming, then predicting based on that picture? I remember looking into these things about ten years ago, and there were some cool things being done with various scattering methods and with AFM, but am not sure now what is the state of that art. It would seem to me that crystallization is the search for intermolecular docking sites of sufficiently good (albeit presumably weak) affinity and consistent with the formation of a 3D lattice. I wonder what the affinity of these sites is, actually—I guess somewhere in the micromolar range, based on usual protein concentrations under crystallization conditions (10 mg/ml of a 40 kD protein is 250 uM). Presumably the various docking sites would change affinity based on the crystallization conditions, which would explain why some crystallization conditions work, others don’t? Maybe a systematic look at all crystallization contacts in the PDB might yield some insight into crystallization? Maybe it’s already been done? JPK ________________________________ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
