On thus topic, I note that the "ModelCIF" format has been developed which allows inclusion of appropriate parameters associated with predicted models, such as those from AlphaFold (e.g. confidence values instead of B-values).
Would it be too much to ask for fields associated with "modelled but not seen" parts of a model to be included in this expanded format (or even in the normal PDBx/mmcif dictionary)? Harry -- Dr Harry Powell > On 10 Mar 2023, at 20:15, Dale Tronrud <[email protected]> wrote: > > Hi > > As a frequent contributor to prior discussions on this same topic I would > like to broaden the discussion a bit. I'm sorry to say that most of the > comments on this threat are exactly the same positions that have been > expressed many times over the years. I don't want to spent time, again, > retyping my opinions on how I prefer to torment the parameters of my models > to express what I believe is going on inside my crystals. > > The fundamental problem is that the parameters we are forced to use, in our > PDB depositions and in the refinement and model building programs available > to us, are wholly inadequate. We cannot accurately (or precisely) describe > what we are are envisioning for the surface side chains, and sometimes entire > stretches of main chain, in our proteins. We can continue to argue with each > other year after year, but there is no solution to this problem other than > changing the nature of PDB models and allowing a reasonable description of > multi-conformation models. > > I believe it is fair to say that the consensus after a previous round of > this discussion was that, at the very least, we need a flag for each atom > which indicates whether that atom was placed based on electron density or > simply to make a chemically complete set of atoms for that type of monomer. > I haven't looked but I think that was about five or ten years ago. Since > then the PDB has made major changes to the structure of PDB entries that will > require most software for analysis of macromolecular models be rewritten and > right now that organization is making a major push to get us to virtually > attend a workshop to help us make this transition. And yet I don't think > there is anything in this new data dictionary to help us with this important > but intractable problem. > > Unless the PDB gives us the parameters we need to properly describe a > macromolecular model, and the refinement/model building developers give us > the tools to make use of them, we will be back here again, every five years > or so, rehashing this debate over exactly the same, irreconcilably poor, > solutions to this problem. > > Dale E. Tronrud > > >> On 3/10/2023 1:05 AM, Julia Griese wrote: >> Hi all, >> My impression has been that the most common approach these days is to “let >> the B-factors take care of it”, but I might be wrong. Maybe it’s time to run >> another poll? >> Personally, I call any other approach R-factor cosmetics. The goal in model >> building is not to achieve the lowest possible R-factors, it’s to build the >> most physically meaningful, most likely to be correct, model. So if you know >> that the side chain is part of the protein, you should model it the best way >> you can. If it’s there, just disordered, then the most correct way to model >> it is to let it have high B-factors. Most molecular graphics programs don’t >> flag zero-occupancy atoms, so the user might never notice. Truncation of a >> side chain, unless there is evidence that it really physically isn’t there, >> is also misleading, in my opinion. I don’t believe that it is more helpful >> to the non-expert user than high B-factors either. >> If people who are not structural biologists themselves don’t know how to use >> a structure, then we need to educate them better. It is very straightforward >> these days to look at electron density in the PDB viewer. It used to be >> difficult, but nowadays there’s no excuse for not checking the electron >> density. The PDB validation flags RSRZ outliers. You can easily colour a >> structure by B-factors. It doesn’t take that much effort to teach students >> how to validate structures. The main point you need to get across is that it >> is necessary to do so. And this needs to be done not only in courses aimed >> at prospective experimental structural biologists, of course, but whenever >> students use structures in any way. >> This is just the opinion of someone who feels very strongly about teaching >> structure validation and rejoices when students’ reply to the question “What >> was the most important thing you learned today?” is: “Don’t blindly trust >> anything.” >> Cheers >> /Julia >> -- >> Dr. Julia Griese >> Associate Professor (Docent) >> Principal Investigator >> Department of Cell and Molecular Biology >> Uppsala University >> BMC, Box 596 >> SE-75124 Uppsala >> Sweden >> email: [email protected] >> phone: +46-(0)18-471 4982 >> http://www.icm.uu.se/structural-biology/griese-lab/ >> <http://www.icm.uu.se/structural-biology/griese-lab/> >> *From: *CCP4 bulletin board <[email protected]> on behalf of Bernhard >> Lechtenberg <[email protected]> >> *Reply-To: *Bernhard Lechtenberg <[email protected]> >> *Date: *Friday, March 10, 2023 at 05:07 >> *To: *"[email protected]" <[email protected]> >> *Subject: *Re: [ccp4bb] To Trim or Not to To Trim >> I found the poll I wrote about earlier. This actually is way older than I >> had expected (2011). You can see the poll results (which was run by Ed >> Pozharski) and discussion at the time here in the CCP4BB archive: >> https://www.mail-archive.com/[email protected]/msg20268.html >> <https://www.mail-archive.com/[email protected]/msg20268.html> >> In brief, the results of 240 respondents were: >> Delete the atoms 43% >> Let refinement take care of it by inflating B-factors 41% >> Set occupancy to zero 12% >> Other 4% >> Bernhard >> *From: *CCP4 bulletin board <[email protected]> on behalf of Debanu Das >> <[email protected]> >> *Date: *Friday, 10 March 2023 at 2:56 pm >> *To: *[email protected] <[email protected]> >> *Subject: *Re: [ccp4bb] To Trim or Not to To Trim >> We dealt with this in-depth during structural genomics days when we >> deposited over 1500 novel, high-quality, experimentally-phased structures >> into the PDB. Think it’s prudent to trim/truncate side chains without >> reliable density. >> Non-structural biologists using PDB structures without expert help can err >> in any of these scenarios: misinterpreting most common/random rotamer, zero >> occupancy atoms, B-factors, etc. >> What is the value of populating the PDB, which is a structural model >> repository, with such information that is not there, i.e., reliable >> structural model? >> Any trained crystallographer/structural biologist can easily add in side >> chain information if needed for modeling/computational chemistry reasons. >> Best regards, >> Debanu >> On Thu, Mar 9, 2023 at 6:50 PM Jurgen Bosch <[email protected] >> <mailto:[email protected]>> wrote: >> I’d say no trimming to side chains for the following reason: There >> are non-structural biologists using PDB files and if atoms are >> missing they don’t know what to do. A better approach is where no >> side chain density allows support of placement, pick the most common >> rotamer and set the occupancy to zero for those atoms lacking >> density support. More work for you but more accurate in my opinion. >> Jürgen >> _______________________________________________ >> Jürgen Bosch, PhD, MBA >> Center for Global Health & Diseases >> Case Western Reserve University >> Cleveland, OH 44106 >> https://www.linkedin.com/in/jubosch/ >> <https://www.linkedin.com/in/jubosch/> >> CEO & Co-Founder at InterRayBio, LLC >> On Mar 9, 2023, at 9:45 PM, Bernhard Lechtenberg >> <[email protected] >> <mailto:[email protected]>> wrote: >> Hi Rhys, >> I am also all for leaving side chains and letting the B-factors >> deal with the weak/absent density. >> I don’t think there is a consensus, but I kind of remember that >> somebody did a poll a few years ago and if I remember correctly >> the main approaches were the one described above, or trimming >> the side-chains. >> Bernhard >> *Bernhard C. Lechtenberg* PhD >> NHMRC Emerging Leadership Fellow >> Laboratory Head >> Ubiquitin Signalling Division >> E [email protected] <mailto:[email protected]> >> T +61 3 9345 2217 >> *From: *CCP4 bulletin board <[email protected] >> <mailto:[email protected]>> on behalf of Rhys Grinter >> <[email protected] >> <mailto:[email protected]>> >> *Date: *Friday, 10 March 2023 at 12:26 pm >> *To: *[email protected] <mailto:[email protected]> >> <[email protected] <mailto:[email protected]>> >> *Subject: *[ccp4bb] To Trim or Not to To Trim >> Hi All, >> I'm trying to crowdsource an opinion on how people deal with >> modelling side chains with poorly resolved electron or cryoEM >> density. >> My preference is to model the sidechain and allow the B-factors >> to go high in refinement to represent that the side chain is >> flexible. However, I'm aware that some people truncate >> sidechains if density is not present to justify modelling. I've >> also seen models where the sidechain is modelled but with zero >> occupancy if density isn't present. >> Is there a consensus and justifying arguments for why one >> approach is better? >> Cheers, >> Rhys >> >> ------------------------------------------------------------------------ >> 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> >> -- >> --- >> LinkedIn: www.linkedin.com/in/debanudas >> <http://www.linkedin.com/in/debanudas> >> Cal Alumni: cal.berkeley.edu/debanudas <http://cal.berkeley.edu/debanudas> >> ------------------------------------------------------------------------ >> 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> >> VARNING:Klicka inte på länkar och öppna inte bilagor om du inte känner igen >> avsändaren och vet att innehållet är säkert. >> CAUTION:Do not click on links or open attachments unless you recognise the >> sender and know the content is safe. >> Page Title >> När du har kontakt med oss på Uppsala universitet med e-post så innebär det >> att vi behandlar dina personuppgifter. 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