Hi Saif, Whilst in very general terms, ∆Tm does correlate with binding affinity (there will of course always be exceptions to this rule), I don't think there is a cutoff beyond which you know that co-crystallisation is feasible. The degree of stabilisation will depend very much on the system you are studying.
I've had proteins crystallise with ligands with a very modest ∆Tms (1-2ºC) and then failed to get the same protein to crystallise with ligands that give a 15-20ºC ∆Tm. I certainly wouldn't let a TSA result dissuade me from trying to co-crystallise a protein with a ligand if the hoped-for structure was important for answering whatever biological question I'm asking. Good luck, Dave -- Dr David C. Briggs Senior Laboratory Research Scientist Signalling and Structural Biology Lab The Francis Crick Institute London, UK == Diamond User Committee MX representative == about.me/david_briggs ________________________________ From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of Saif Mohd <saif.biotec...@gmail.com> Sent: 25 February 2021 14:55 To: CCP4BB@JISCMAIL.AC.UK <CCP4BB@JISCMAIL.AC.UK> Subject: [ccp4bb] Co-crystallization and thermal shift assay Hello everyone, 1) How much change in Tm (ΔTm) in a thermal shift assay is considered to be significant ? 2) A negative ΔTm infers that the compound is making the protein unstable. In such a case, will the co-crystallization be difficult or just impossible or on the contrary it shouldn't matter much? Thanks and best regards, Saif ________________________________ To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1<https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.jiscmail.ac.uk%2Fcgi-bin%2FWA-JISC.exe%3FSUBED1%3DCCP4BB%26A%3D1&data=04%7C01%7C%7C3edf5b78edec49c9538708d8d99d7c42%7C4eed7807ebad415aa7a99170947f4eae%7C0%7C1%7C637498617699057063%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=tZzKYoUHHoSDDlf4Cjp5DRFk5z0XqUXl4rFJKgJJS2A%3D&reserved=0> The Francis Crick Institute Limited is a registered charity in England and Wales no. 1140062 and a company registered in England and Wales no. 06885462, with its registered office at 1 Midland Road London NW1 1AT ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
