Hi Ramaswamy I assume this is an April Fool's but it's still a serious question because many reviewers who are not crystallographers or electron microscopists may not fully appreciate the difference currently between the precision of structures obtained by experimental and predictive methods, though the latter are certainly catching up. The answer of course lies in the mean co-ordinate precision, related to the map resolution.
Quoting https://people.cryst.bbk.ac.uk/~ubcg05m/precgrant.html : "The accuracy and precision required of an experimentally determined model of a macromolecule depends on the biological questions being asked of the structure. Questions involving the overall fold of a protein, or its topological similarity to other proteins, can be answered by structures of fairly low precision such as those obtained from very low resolution X-ray crystal diffraction data [or AlphaFold]. Questions involving reaction mechanisms require much greater accuracy and precision as obtained from well-refined, high-resolution X-ray structures, including proper statistical analyses of the standard uncertainties (*s.u.'s*) of atomic positions and bond lengths.". According to https://www.nature.com/articles/s41586-021-03819-2 : The accuracy of AlphaFold structures at the time of writing (2021) was around 1.0 Ang. RMSD for main-chain and 1.5 Ang. RMSD for side-chain atoms and probably hasn't changed much since. This is described as "highly accurate"; however this only means that AlphaFold's accuracy is much higher in comparison with other prediction methods, not in comparison with experimental methods. Also note that AlphaFold's accuracy is estimated by comparison with the X-ray structure which remains the "gold standard"; there's no way (AFAIK) of independently assessing AlphaFold's accuracy or precision. Quoting https://scripts.iucr.org/cgi-bin/paper?S0907444998012645 : "Data of 0.94 A resolution for the 237-residue protein concanavalin A are used in unrestrained and restrained full-matrix inversions to provide standard uncertainties sigma(r) for positions and sigma(l) for bond lengths. sigma(r) is as small as 0.01 A for atoms with low Debye B values but increases strongly with B." There's a yawning gap between 1.0 - 1.5 Ang. and 0.01 Ang.! Perhaps AlphaFold structures should be deposited using James Holton's new PDB format (now that is an April Fool's !). One final suggestion for a reference in your grant application: https://www.biorxiv.org/content/10.1101/2022.03.08.483439v2 . Cheers -- Ian On Sat, 1 Apr 2023 at 13:06, Subramanian, Ramaswamy <subra...@purdue.edu> wrote: > Dear All, > > I am unsure if all other groups will get it - but I am sure this group > will understand the frustration. > > My NIH grant did not get funded. A few genuine comments - they make > excellent sense. We will fix that. > > One major comment is, “Structures can be predicted by alpfafold and other > software accurately, so the effort put on the grant to get structures by > X-ray crystallography/cryo-EM is not justified.” > > The problem is when a company with billions of $$s develops a method and > blasts it everywhere - the message is so pervasive… > > *Question: I*s there a canned consensus paragraph that one can add with > references to grants with structural biology (especially if the review > group is not a structural biology group) to say why the most modern > structure prediction programs are not a substitute for structural work? > > Thanks. > > > Rams > subra...@purdue.edu > > > > > ------------------------------ > > 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/
