Hard but not impossible - even when you *are* fitting to low-res density. See https://twitter.com/crolltristan/status/1381258326223290373?s=21 for example - no Ramachandran outliers, 1.3% sidechain outliers, clashscore of 2... yet multiple regions out of register by anywhere up to 15 residues! I never publicly named the structure (although I did share my rebuilt model with the authors), but the videos and images in that thread should be enough to illustrate the scale of the problem.
And that was *with* a map to fit! Take away the map, and run some MD energy minimisation (perhaps with added Ramachandran and rotamer restraints), and I think it would be easy to get your model to fool most “simple” validation metrics (please don’t actually do this). The upshot is that I still think validation of predicted models in the absence of at least moderate-resolution experimental data is still a major challenge requiring very careful thought. — Tristan On 13 Jan 2022, at 18:41, James Holton <jmhol...@lbl.gov<mailto:jmhol...@lbl.gov>> wrote: Agree with Pavel. Something I think worth adding is a reminder that the MolProbity score only looks at bad clashes, ramachandran and rotamer outliers. MPscore=0.426∗ln(1+clashscore)+0.33∗ln(1+max(0,rota_out−1))+0.25∗ln(1+max(0,rama_iffy−2))+0.5 It pays no attention whatsoever to twisted peptide bonds, C-beta deviations, and, for that matter, bond lengths and bond angles. If you tweak your weights right you can get excellent MP scores, but horrible "geometry" in the traditional bonds-and-angles sense. The logic behind this kind of validation is that normally nonbonds and torsions are much softer than bond and angle restraints and therefore fertile ground for detecting problems. Thus far, I am not aware of any "Grand Unified Score" that combines all geometric considerations, but perhaps it is time for one? Tristan's trivial solution aside, it is actually very hard to make all the "geometry" ideal for a real-world fold, and especially difficult to do without also screwing up the agreement with density (R factor). I would argue that if you don't have an R factor then you should get one, but I am interested in opinions about alternatives. I.E. What if we could train an AI to predict Rfree by looking at the coordinates? -James Holton MAD Scientist On 12/21/2021 9:25 AM, Pavel Afonine wrote: Hi Reza, If you think about it this way... Validation is making sure that the model makes sense, data make sense and model-to-data fit make sense, then the answer to your question is obvious: in your case you do not have experimental data (at least in a way we used to think of it) and so then of these three validation items you only have one, which, for example, means you don’t have to report things like R-factors or completeness in high-resolution shell. Really, the geometry of an alpha helix does not depend on how you determined it: using X-rays or cryo-EM or something else! So, most (if not all) model validation tools still apply. Pavel On Mon, Dec 20, 2021 at 8:10 AM Reza Khayat <rkha...@ccny.cuny.edu<mailto:rkha...@ccny.cuny.edu>> wrote: Hi, Can anyone suggest how to validate a predicted structure? Something similar to wwPDB validation without the need for refinement statistics. I realize this is a strange question given that the geometry of the model is anticipated to be fine if the structure was predicted by a server that minimizes the geometry to improve its statistics. Nonetheless, the journal has asked me for such a report. Thanks. Best wishes, Reza Reza Khayat, PhD Associate Professor City College of New York Department of Chemistry and Biochemistry New York, NY 10031 ________________________________ 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/
