Dear all,
Thank you for the responses. My question regarding validation was not directed at weather the prediction was correct (i.e. sufficiently comparable to the experimentally determined structure). I realize this question in itself is not easily answered. I also agree with what everyone has written below. My question was regarding the geometry of the structure. I also understand that outstanding geometry does not indicate an accurately predicted structure -the helix example indicated by Tristian. Nonetheless, the server links sent earlier are extremely helpful. Reza Khayat, PhD Associate Professor City College of New York Department of Chemistry and Biochemistry New York, NY 10031 ________________________________ From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of F.Xavier Gomis-Rüth <xgr...@ibmb.csic.es> Sent: Tuesday, December 21, 2021 5:04 AM To: CCP4BB@JISCMAIL.AC.UK Subject: [EXTERNAL] [ccp4bb] Fwd: [ccp4bb] Validation of structure prediction Dear all, this is by far not the general case in our hands. Depending on which AlphaFold protocol is used, the resulting models have locally disfavourable geometries–including clashes–, impossible chain crossovers, etc. I would definitively recommend everybody to go through the model in detail and perform a final geometry minimization with Coot and/or Phenix/Refmac. And in these cases, general geometry validation as provided by MolProbity provides a final proof of the computational model. Best, Xavier -------- Forwarded Message -------- Subject: Re: [ccp4bb] Validation of structure prediction Date: Tue, 21 Dec 2021 09:43:37 +0000 From: Vollmar, Melanie (DLSLtd,RAL,LSCI) <000064fe7ccc6b4d-dmarc-requ...@jiscmail.ac.uk><mailto:000064fe7ccc6b4d-dmarc-requ...@jiscmail.ac.uk> Reply-To: Vollmar, Melanie (DLSLtd,RAL,LSCI) <melanie.voll...@diamond.ac.uk><mailto:melanie.voll...@diamond.ac.uk> To: CCP4BB@JISCMAIL.AC.UK<mailto:CCP4BB@JISCMAIL.AC.UK> Tristan is spot on. All the predicted structures have near perfect geometry, so commonly used validation tools like MolProbity can no longer be applied. What you need to consider is biological relevance of the predicted model. Does the model correctly reflect residue arrangement in the active site? Are domains in correct relative orientation to allow for interactions and movements, perhaps found by some other assay? Is there appropriate room to fit a ligand/cofactor? Are transmembrane helices, if there are any, correctly found? You need to map the knowledge you have of your protein to the structure and see if the atom positions and what you know support each other. Cheers M ________________________________ From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK><mailto:CCP4BB@JISCMAIL.AC.UK> on behalf of Tristan Croll <ti...@cam.ac.uk><mailto:ti...@cam.ac.uk> Sent: 21 December 2021 08:28 To: CCP4BB@JISCMAIL.AC.UK<mailto:CCP4BB@JISCMAIL.AC.UK> <CCP4BB@JISCMAIL.AC.UK><mailto:CCP4BB@JISCMAIL.AC.UK> Subject: Re: [ccp4bb] Validation of structure prediction I agree with Dale. Tools like MolProbity are not the right approach to validating a structure prediction. To understand why, just consider that all you need to do to get a perfect MolProbity score is predict every structure as a single long alpha helix with ideal rotamers, with a kink at each proline. To validate a predicted structure will require a completely different toolset - one that I’m not sure fully exists yet. — Tristan > On 20 Dec 2021, at 18:47, Dale Tronrud > <de...@daletronrud.com><mailto:de...@daletronrud.com> wrote: > > I don't see any reason to believe that software designed to validate > crystallographic or NMR models would have any utility validating AlphaFold > predicted models. Doesn't the prediction software already ensure that all > the indicators used by Molprobity are obeyed? I'm afraid that the tools to > validate any new technique must be designed specifically for that technique. > (And when they become available they will be useless for validating > crystallographic models!) > > Dale E. Tronrud > >> On 12/20/2021 10:28 AM, Nicholas Clark wrote: >> The Molprobity server can be run online and only requires the coordinates in >> PDB format: >> http://molprobity.biochem.duke.edu/<https://urldefense.proofpoint.com/v2/url?u=http-3A__molprobity.biochem.duke.edu_&d=DwMDaQ&c=4NmamNZG3KTnUCoC6InoLJ6KV1tbVKrkZXHRwtIMGmo&r=1DzJFW0v6TgEhkW1gy_-ke-RbtvS1fzEbD5_hcb9Up0&m=Ore7pZl_g57-Bha3m6bv3ayt12QpXPz1lbBlJYIx0rY&s=ekPRcBIEvpMpSOCQ3Iwa3WeIz5hew6AEXPmRUbWF9eg&e=> >> >> <http://molprobity.biochem.duke.edu/<https://urldefense.proofpoint.com/v2/url?u=http-3A__molprobity.biochem.duke.edu_&d=DwMDaQ&c=4NmamNZG3KTnUCoC6InoLJ6KV1tbVKrkZXHRwtIMGmo&r=1DzJFW0v6TgEhkW1gy_-ke-RbtvS1fzEbD5_hcb9Up0&m=Ore7pZl_g57-Bha3m6bv3ayt12QpXPz1lbBlJYIx0rY&s=ekPRcBIEvpMpSOCQ3Iwa3WeIz5hew6AEXPmRUbWF9eg&e=>>. >> Best, >> Nick Clark >> On Mon, Dec 20, 2021 at 11:10 AM Reza Khayat >> <rkha...@ccny.cuny.edu<mailto: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<https://urldefense.proofpoint.com/v2/url?u=https-3A__www.jiscmail.ac.uk_cgi-2Dbin_WA-2DJISC.exe-3FSUBED1-3DCCP4BB-26A-3D1&d=DwMDaQ&c=4NmamNZG3KTnUCoC6InoLJ6KV1tbVKrkZXHRwtIMGmo&r=1DzJFW0v6TgEhkW1gy_-ke-RbtvS1fzEbD5_hcb9Up0&m=Ore7pZl_g57-Bha3m6bv3ayt12QpXPz1lbBlJYIx0rY&s=hWNjcApPyf1FTiKmHVXQtOyKoG_797_TjQ3S8Qt2ZqI&e=> >> >> <https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1<https://urldefense.proofpoint.com/v2/url?u=https-3A__www.jiscmail.ac.uk_cgi-2Dbin_WA-2DJISC.exe-3FSUBED1-3DCCP4BB-26A-3D1&d=DwMDaQ&c=4NmamNZG3KTnUCoC6InoLJ6KV1tbVKrkZXHRwtIMGmo&r=1DzJFW0v6TgEhkW1gy_-ke-RbtvS1fzEbD5_hcb9Up0&m=Ore7pZl_g57-Bha3m6bv3ayt12QpXPz1lbBlJYIx0rY&s=hWNjcApPyf1FTiKmHVXQtOyKoG_797_TjQ3S8Qt2ZqI&e=>> >> -- >> Nicholas D. 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