Since I didn’t actually read the press release (but “attended" the CASP event instead where the results were discussed in a little more detail…) this is news to me, but I’d agree that there is some hyperbole there.
Alphafold2 (it’s probably important to distinguish it from AlphaFold since it’s a complete re-write, from what I understand) was the only software that reliably gave results that could be used for MR. I don’t know how long it actually took to run the modelling for each sequence (building its libraries was, shall we say, “time-consuming”), but it may not be a bad way to get an MR model if you can get DeepMind to run the modelling for you. Harry > On 8 Dec 2020, at 13:04, Ian Tickle <ianj...@gmail.com> wrote: > > > There was a little bit of press-release hype: the release stated "a score of > around 90 GDT is informally considered to be competitive with results > obtained from experimental methods" and "our latest AlphaFold system achieves > a median score of 92.4 GDT overall across all targets. This means that our > predictions have an average error (RMSD) of approximately 1.6 Angstroms,". > > Experimental methods achieve an average error of around 0.2 Ang. or better at > 2 Ang. resolution, and of course much better at atomic resolution (1 Ang. or > better), or around 0.5 Ang. at 3 Ang. resolution. For ligand-binding studies > I would say you need 3 Ang. resolution or better. 1.6 Ang. error is probably > equivalent to around 4 Ang. resolution. No doubt that will improve with time > and experience, though I think it will be an uphill struggle to get better > than 1 Ang. error, simply because the method can't be better than the data > that go into it and 1-1.5 Ang. represents a typical spread of homologous > models in the PDB. So yes very competitive if you're desperate for a MR > starting model, but not quite yet there for a refined high-resolution > structure. > > Cheers > > -- Ian > > > On Tue, 8 Dec 2020 at 12:11, Harry Powell - CCP4BB > <0000193323b1e616-dmarc-requ...@jiscmail.ac.uk> wrote: > Hi > > It’s a bit more than science by press release - they took part in CASP14 > where they were given sequences but no other experimental data, and did > significantly better than the other homology modellers (who had access to the > same data) when judge by independent analysis. There were things wrong with > their structures, sure, but in almost every case they were less wrong than > the other modellers (many of whom have been working on this problem for > decades). > > It _will_ be more impressive once the methods they used (or equivalents) are > implemented by other groups and are available to the “public” (I haven’t > found an AlphaFold webserver to submit a sequence to, whereas the other > groups in the field do make their methods readily available), but it’s still > a step-change in protein structure prediction - it shows it can be done > pretty well. > > Michel is right, of course; you can’t have homology modelling without > homologous models, which are drawn from the PDB - but the other modellers had > the same access to the PDB (just as we all do…). > > Just my two ha’porth. > > Harry > > > On 8 Dec 2020, at 11:33, Goldman, Adrian <adrian.gold...@helsinki.fi> wrote: > > > > My impression is that they haven’t published the code, and it is science by > > press-release. If one of us tried it, we would - rightly - get hounded out > > of time. > > > > Adrian > > > > > > > >> On 4 Dec 2020, at 15:57, Michel Fodje <michel.fo...@lightsource.ca> wrote: > >> > >> I think the results from AlphaFold2, although exciting and a breakthrough > >> are being exaggerated just a bit. We know that all the information > >> required for the 3D structure is in the sequence. The protein folding > >> problem is simply how to go from a sequence to the 3D structure. This is > >> not a complex problem in the sense that cells solve it deterministically. > >> Thus the problem is due to lack of understanding and not due to > >> complexity. AlphaFold and all the others trying to solve this problem are > >> “cheating” in that they are not just using the sequence, they are using > >> other sequences like it (multiple-sequence alignments), and they are using > >> all the structural information contained in the PDB. All of this > >> information is not used by the cells. In short, unless AlphaFold2 now > >> allows us to understand how exactly a single protein sequence produces a > >> particular 3D structure, the protein folding problem is hardly solved in a > >> theoretical sense. The only reason we know how well AlphaFold2 did is > >> because the structures were solved and we could compare with the > >> predictions, which means verification is lacking. > >> > >> The protein folding problem will be solved when we understand how to go > >> from a sequence to a structure, and can verify a given structure to be > >> correct without experimental data. Even if AlphaFold2 got 99% of > >> structures right, your next interesting target protein might be the 1%. > >> How would you know? Until then, what AlphaFold2 is telling us right now > >> is that all (most) of the information present in the sequence that > >> determines the 3D structure can be gleaned in bits and pieces scattered > >> between homologous sequences, multiple-sequence alignments, and other > >> protein 3D structures in the PDB. Deep Learning allows a huge amount of > >> data to be thrown at a problem and the back-propagation of the networks > >> then allows careful fine-tuning of weights which determine how relevant > >> different pieces of information are to the prediction. The networks used > >> here are humongous and a detailed look at the weights (if at all feasible) > >> may point us in the right direction. > >> > >> > >> From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> On Behalf Of Nave, Colin > >> (DLSLtd,RAL,LSCI) > >> Sent: December 4, 2020 9:14 AM > >> To: CCP4BB@JISCMAIL.AC.UK > >> Subject: External: Re: [ccp4bb] AlphaFold: more thinking and less > >> pipetting (?) > >> > >> The subject line for Isabel’s email is very good. > >> > >> I do have a question (more a request) for the more computer scientist > >> oriented people. I think it is relevant for where this technology will be > >> going. It comes from trying to understand whether problems addressed by > >> Alpha are NP, NP hard, NP complete etc. My understanding is that the > >> previous successes of Alpha were for complete information games such as > >> Chess and Go. Both the rules and the present position were available to > >> both sides. The folding problem might be in a different category. It would > >> be nice if someone could explain the difference (if any) between Go and > >> the protein folding problem perhaps using the NP type categories. > >> > >> Colin > >> > >> > >> > >> From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> On Behalf Of Isabel > >> Garcia-Saez > >> Sent: 03 December 2020 11:18 > >> To: CCP4BB@JISCMAIL.AC.UK > >> Subject: [ccp4bb] AlphaFold: more thinking and less pipetting (?) > >> > >> 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 > >> > >> 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 > >> FAX: 00 33 (0) 476 50 18 90 > >> 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 > >> > >> > >> > >> -- > >> > >> This e-mail and any attachments may contain confidential, copyright and or > >> privileged material, and are for the use of the intended addressee only. > >> If you are not the intended addressee or an authorised recipient of the > >> addressee please notify us of receipt by returning the e-mail and do not > >> use, copy, retain, distribute or disclose the information in or attached > >> to the e-mail. > >> Any opinions expressed within this e-mail are those of the individual and > >> not necessarily of Diamond Light Source Ltd. > >> Diamond Light Source Ltd. cannot guarantee that this e-mail or any > >> attachments are free from viruses and we cannot accept liability for any > >> damage which you may sustain as a result of software viruses which may be > >> transmitted in or with the message. > >> Diamond Light Source Limited (company no. 4375679). Registered in England > >> and Wales with its registered office at Diamond House, Harwell Science and > >> Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom > >> > >> > >> > >> To unsubscribe from the CCP4BB list, click the following link: > >> 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 > >> > > > > > > To unsubscribe from the CCP4BB list, click the following link: > > 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 > > 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/ ######################################################################## 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/
