Biophysical techniques used to screen samples (e.g. SEC, SEC-MALS, DLS, SAXS, CD...) before freezing are not as promising as many hope for. There are lots of examples where samples behave beautiful by multiple biophysics methods and then crash and burn on a cryo-EM grid. Consequently, screening freezing conditions become the bottle neck of cryo-EM.
? Reza Khayat, PhD Assistant Professor City College of New York Department of Chemistry New York, NY 10031 ________________________________ From: CCP4 bulletin board <[email protected]> on behalf of Patrick Shaw Stewart <[email protected]> Sent: Tuesday, July 23, 2019 1:35 PM To: [email protected] Subject: [EXTERNAL] Re: [ccp4bb] challenges in structural biology On a completely different tack, isn't the most pressing requirement in current structural biology a really good method of characterizing macromolecular samples before they are put onto cryoEM grids - ie analysing and screening them in solution. For one thing I'm told those huge microscopes are quite prone to breaking down, which makes the queues (lines) to get onto them even longer. That method might be (micro-scale) DLS - or something completely different. Thx, Patrick On Mon, Jul 15, 2019 at 8:44 PM Holton, James M <[email protected]<mailto:[email protected]>> wrote: Hello folks, I have the distinct honor of chairing the next Gordon Research Conference on Diffraction Methods in Structural Biology (July 26-31 2020). This meeting will focus on the biggest challenges currently faced by structural biologists, and I mean actual real-world challenges. As much as possible, these challenges will take the form of friendly competitions with defined parameters, data, a scoring system, and "winners", to be established along with other unpublished results only at the meeting, as is tradition at GRCs. But what are the principle challenges in biological structure determination today? I of course have my own ideas, but I feel like I'm forgetting something. Obvious choices are: 1) getting crystals to diffract better 2) building models into low-resolution maps (after failing at #1) 3) telling if a ligand is really there or not 4) the phase problem (dealing with weak signal, twinning and pseudotranslation) 5) what does "resolution" really mean? 6) why are macromolecular R factors so much higher than small-molecule ones? 7) what is the best way to process serial crystallography data? 8) how should one deal with non-isomorphism in multi-crystal methods? 9) what is the "structure" of something that won't sit still? What am I missing? Is industry facing different problems than academics? Are there specific challenges facing electron-based techniques? If so, could the combined strength of all the world's methods developers solve them? I'm interested in hearing the voice of this community. On or off-list is fine. -James Holton MAD Scientist ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1<https://urldefense.proofpoint.com/v2/url?u=https-3A__www.jiscmail.ac.uk_cgi-2Dbin_webadmin-3FSUBED1-3DCCP4BB-26A-3D1&d=DwMFaQ&c=4NmamNZG3KTnUCoC6InoLJ6KV1tbVKrkZXHRwtIMGmo&r=1DzJFW0v6TgEhkW1gy_-ke-RbtvS1fzEbD5_hcb9Up0&m=5O3I_98NbuDcvYfKfDd3xVASHjtAMAvRVBbzCOA_CzQ&s=C8mKEvBkz3Ot9Z6OAvg9dRGW_nPkNtKthPtD-AtpxXg&e=> -- [email protected]<mailto:[email protected]> Douglas Instruments Ltd. Douglas House, East Garston, Hungerford, Berkshire, RG17 7HD, UK Directors: Peter Baldock, Patrick Shaw Stewart http://www.douglas.co.uk<https://urldefense.proofpoint.com/v2/url?u=http-3A__www.douglas.co.uk&d=DwMFaQ&c=4NmamNZG3KTnUCoC6InoLJ6KV1tbVKrkZXHRwtIMGmo&r=1DzJFW0v6TgEhkW1gy_-ke-RbtvS1fzEbD5_hcb9Up0&m=5O3I_98NbuDcvYfKfDd3xVASHjtAMAvRVBbzCOA_CzQ&s=5JrRvpu7e7luDbqFq5Mt3CAmoFnJNdgdpvFuZOvpMOA&e=> Tel: 44 (0) 148-864-9090 US toll-free 1-877-225-2034 Regd. England 2177994, VAT Reg. GB 480 7371 36 ________________________________ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1<https://urldefense.proofpoint.com/v2/url?u=https-3A__www.jiscmail.ac.uk_cgi-2Dbin_webadmin-3FSUBED1-3DCCP4BB-26A-3D1&d=DwMFaQ&c=4NmamNZG3KTnUCoC6InoLJ6KV1tbVKrkZXHRwtIMGmo&r=1DzJFW0v6TgEhkW1gy_-ke-RbtvS1fzEbD5_hcb9Up0&m=5O3I_98NbuDcvYfKfDd3xVASHjtAMAvRVBbzCOA_CzQ&s=C8mKEvBkz3Ot9Z6OAvg9dRGW_nPkNtKthPtD-AtpxXg&e=> ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
