I agree completely Tom. Having been recently involved in some efforts to identify interesting compounds against SARS-CoV-2, I can say that the current AI/ML methods for docking/predicting small molecule binding have very very low success rates (I’m being generous here), even when you are working with the experimental protein structure! Maybe this is the next frontier for the prediction methods (after they’ve solved the protein/protein complex problem of course), but it seems there is a long way to go.
Given that many structures are solved to look at their interaction with other proteins or small molecules I think that experimental structural biology is here to stay for a while - past Tom’s retirement even! However, will these fairly accurate protein predictions make experimental phasing a thing of the past? > On Dec 3, 2020, at 4:16 PM, Peat, Tom (Manufacturing, Parkville) > <tom.p...@csiro.au> wrote: > > Although they can now get the fold correct, I don't think they have all the > side chain placement so perfect as to be able to predict the fold and how a > compound or another protein binds, so we can still do complexes. I don't know > what others end up spending their time doing, but much of my work has been > trying to fit ligands into density, which may take another few years of > algorithm development, which is fine for me as I can retire! > cheers, tom > > Tom Peat, PhD > Proteins Group > Biomedical Program, CSIRO > 343 Royal Parade > Parkville, VIC, 3052 > +613 9662 7304 > +614 57 539 419 > tom.p...@csiro.au <mailto:tom.p...@csiro.au> > > From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK > <mailto:CCP4BB@JISCMAIL.AC.UK>> on behalf of Jon Cooper > <0000488a26d62010-dmarc-requ...@jiscmail.ac.uk > <mailto:0000488a26d62010-dmarc-requ...@jiscmail.ac.uk>> > Sent: Friday, December 4, 2020 9:55 AM > To: CCP4BB@JISCMAIL.AC.UK <mailto:CCP4BB@JISCMAIL.AC.UK> > <CCP4BB@JISCMAIL.AC.UK <mailto:CCP4BB@JISCMAIL.AC.UK>> > Subject: Re: [ccp4bb] AlphaFold: more thinking and less pipetting (?) > > Thanks all, very interesting, so our methods are just needed to identify the > crystallization impurities, when the trays have been thrown away ;- > > Cheers, Jon.C. > > Sent from ProtonMail mobile > > > > -------- Original Message -------- > On 3 Dec 2020, 22:31, Anastassis Perrakis < a.perra...@nki.nl > <mailto:a.perra...@nki.nl>> wrote: > > AlphaFold - or similar ideas that will surface up sooner or later - will > beyond doubt have major impact. The accuracy it demonstrated compared to > others is excellent. > > “Our” target (T1068) that was not solvable by MR with the homologous search > structure or a homology model (it was phased with Archimboldo, rather > easily), is easily solvable with the AlphaFold model as a search model. In > PHASER I get Rotation Z-score 17.9, translation Z-score 26.0, using defaults. > > > imho what remains to be seen is: > > a. how and when will a prediction server be available? > b. even if training needs computing that will surely unaccessible to most, > will there be code that can be installed in a “reasonable” number of GPUs and > how fast will it be? > c. how do model quality metrics (that do not compared with the known answer) > correlate with the expected RMSD? AlphaFold, no matter how impressive, still > gets things wrong. > c. will the AI efforts now gear to ligand (fragment?) prediction with > similarly impressive performance? > > Exciting times. > > A. > > > > >> On 3 Dec 2020, at 21:55, Jon Cooper >> <0000488a26d62010-dmarc-requ...@jiscmail.ac.uk >> <mailto:0000488a26d62010-dmarc-requ...@jiscmail.ac.uk>> wrote: >> >> Hello. A quick look suggests that a lot of the test structures were solved >> by phaser or molrep, suggesting it is a very welcome improvement on homology >> modelling. It would be interesting to know how it performs with structures >> of new or uncertain fold, if there are any left these days. Without >> resorting to jokes about artificial intelligence, I couldn't make that out >> from the CASP14 website or the many excellent articles that have appeared. >> Best wishes, Jon Cooper. >> >> >> Sent from ProtonMail mobile >> >> >> >> -------- Original Message -------- >> On 3 Dec 2020, 11:17, Isabel Garcia-Saez < isabel.gar...@ibs.fr >> <mailto:isabel.gar...@ibs.fr>> wrote: >> >> Dear all, >> >> Just commenting that after the stunning performance of AlphaFold that uses >> AI from Google maybe some of us we could dedicate ourselves to the noble art >> of gardening, baking, doing Chinese Calligraphy, enjoying the clouds pass or >> everything together (just in case I have already prepared my subscription to >> Netflix). >> >> https://www.nature.com/articles/d41586-020-03348-4 >> <https://www.nature.com/articles/d41586-020-03348-4> >> >> Well, I suppose that we still have the structures of complexes (at the >> moment). I am wondering how the labs will have access to this technology in >> the future (would it be for free coming from the company DeepMind - >> Google?). It seems that they have already published some code. Well, >> exciting times. >> >> Cheers, >> >> Isabel >> >> >> Isabel Garcia-Saez PhD >> Institut de Biologie Structurale >> Viral Infection and Cancer Group (VIC)-Cell Division Team >> 71, Avenue des Martyrs >> CS 10090 >> 38044 Grenoble Cedex 9 >> France >> Tel.: 00 33 (0) 457 42 86 15 >> e-mail: isabel.gar...@ibs.fr <mailto:isabel.gar...@ibs.fr> >> FAX: 00 33 (0) 476 50 18 90 >> http://www.ibs.fr/ <http://www.ibs.fr/> >> >> 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://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1> >> 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://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1> > > 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://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1> > > 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://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1> > 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://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1> -- Paul Adams Division Director, Molecular Biophysics & Integrated Bioimaging, LBL (http://biosciences.lbl.gov/divisions/mbib) Principal Investigator, Computational Crystallography Initiative, LBL (http://cci.lbl.gov) Vice President for Technology, the Joint BioEnergy Institute (http://www.jbei.org) Principal Investigator, ALS-ENABLE, Advanced Light Source (http://als-enable.lbl.gov) Division Deputy for Biosciences, Advanced Light Source (https://als.lbl.gov) Laboratory Research Manager, ENIGMA Science Focus Area (http://enigma.lbl.gov) Adjunct Professor, Department of Bioengineering, U.C. Berkeley (http://bioeng.berkeley.edu) Adjunct Professor, Comparative Biochemistry, U.C. Berkeley (http://compbiochem.berkeley.edu) Building 33, Room 250 Building 978, Room 4126 Building 977, Room 180C Tel: 1-510-486-4225 http://cci.lbl.gov/paul <http://cci.lbl.gov/paul> ORCID: 0000-0001-9333-8219 Lawrence Berkeley Laboratory 1 Cyclotron Road BLDG 33R0345 Berkeley, CA 94720, USA. Executive Assistant: Ashley Dawn [ ashleyd...@lbl.gov ][ 1-510-486-5455 ] -- ######################################################################## 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/
