Dear All After about 10 (!) years of (very) hard work we solved the structures of our dearest membrane transporter. Dataset at 2.9 And resolution, fairly anisotropic, experimental phasing, and many looooong nights with Coot and Buster to achieve model refinement.
The experimental structure had a well defined ligand nicely coordinated but also a lipid embedded inside the binding cavity (a complete surprise but biologically relevant) and two detergent molecules well defined (experimental/crystallisation artefact). As our paper was accepted basically when CASP organisers were calling for targets I offered my baby to the computing Gods. However we only provided the sequence to CASP, no info regarding any ligand or lipid. Less than a month after, the CASP team contacted us and send us the best model. In fact it was 2 half models as the transporter is a pseudo dimer, with the N-lobe and C-lobe moving relative to each other during transport cycle, thus divided as two domains in CASP. The results were breathtaking. 0.7 And RSMD on one half, 0.6 on the other. And yes, group 427 was the superpower (did not know at the time that it was AlphaFold). We had long discussions with the CASP team, as -for us- this almost exact modelling was dream-like (or science fiction) and -at some point- we were even suspecting fraud, as our coordinates had travelled over the internet a few times around when interacting with colleagues. The organisers reassured us that we were not the only target that had been “nailed” so no reason to suspect any wrongdoing. To this day I am still baffled and I would be happy to hear from the community, maybe from some of the CASP participants. The target is T024, the “perfect" models are domain-split version (T024-D1 and T024-D2), as AlphaFold2 did not perform so well on the complete assembly. Deposited PDB is 6T1Z Cedric PS: I should also note that many other groups performed very well, much better than I would have dreamed, including on the full protein but just not as crazy-good. — Prof. Cedric Govaerts, Ph.D. Universite Libre de Bruxelles Campus Plaine. Phone :+32 2 650 53 77 Building BC, Room 1C4 203 Boulevard du Triomphe, Acces 2 1050 Brussels Belgium http://govaertslab.ulb.ac.be/ ######################################################################## 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/
