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/ 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 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/ 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 ________________________________ 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 -- --- 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 ________________________________ To unsubscribe from the CCP4BB list, click the following link: 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. 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