Not stupid, but essentially the same as modelling alt confs, though would probably give more overfitting. Alt confs can easily be converted to an ensemble (if done properly…).
Thanks, Nick ——— Nicholas Pearce Assistant Professor in Bioinformatics & DDLS Fellow Linköping University Sweden ________________________________ From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of benjamin bax <ben.d.v....@gmail.com> Sent: Saturday, March 18, 2023 10:07:26 PM To: CCP4BB@JISCMAIL.AC.UK <CCP4BB@JISCMAIL.AC.UK> Subject: Re: [ccp4bb] To Trim or Not to To Trim Hi, Probably a stupid question. Could you multiply a, b and c cell dimensions by 2 or 3 (to give 8 or 27 structures) and restrain well defined parts of structure to be ‘identical’ ? To give you a more NMR like chemically sensible ensemble of structures? Ben > On 18 Mar 2023, at 12:04, Helen Ginn <ccp...@hginn.co.uk> wrote: > > Models for crystallography have two purposes: refinement and interpretation. > Here these two purposes are in conflict. Neither case is handled well by > either trim or not trim scenario, but trimming results in a deficit for > refinement and not-trimming results in a deficit for interpretation. > > Our computational tools are not “fixed” in the same way that the standard > amino acids are “fixed” or your government’s bureaucracy pathways are > “fixed”. They are open for debate and for adjustments. This is a fine example > where it may be more productive to discuss the options for making changes to > the model itself or its representation, to better account for awkward > situations such as these. Otherwise we are left figuring out the best > imperfect way to use an imperfect tool (as all tools are, to varying > degrees!), which isn’t satisfying for enough people, enough of the time. > > I now appreciate the hypocrisy in the argument “do not trim, but also don’t > model disordered regions”, even though I’d be keen to avoid trimming. This > discussion has therefore softened my own viewpoint. > > My refinement models (as implemented in Vagabond) do away with the concept of > B factors precisely for the anguish it causes here, and refines a > distribution of protein conformations which is sampled to generate an > ensemble. By describing the conformations through the torsion angles that > comprise the protein, modelling flexibility of a disordered lysine is > comparatively trivial, and indeed modelling all possible conformations of a > disordered loop becomes feasible. Lysines end up looking like a frayed end of > a rope. Each conformation can produce its own solvent mask, which can be > summed together to produce a blurring of density that matches what you would > expect to see in the crystal. > > In my experience this doesn’t drop the R factors as much as you’d assume, > because blurred out protein density does look very much like solvent, but it > vastly improves the interpretability of the model. This also better models > the boundary between the atoms you would trim and those you’d leave > untrimmed, by avoiding such a binary distinction. No fear of trimming and > pushing those errors unseen into the rest of the structure. No fear of > leaving atoms in with an inadequate B factor model that cannot capture the > nature of the disorder. > > Vagabond is undergoing a heavy rewrite though, and is not yet ready for human > consumption. Its first iteration worked on single-dataset-single-model > refinement, which handled disordered side chains well enough, with no need to > decide to exclude atoms. The heart of the issue lies in main chain > flexibility, and this must be handled correctly, for reasons of > interpretability and elucidating the biological impact. This model isn’t > perfect either, and necessitates its own compromises - but will provide > another tool in the structural biology arsenal. > > —- > > Dr Helen Ginn > Group leader, DESY > Hamburg Advanced Research Centre for Bioorganic Chemistry (HARBOR) > Luruper Chaussee 149 > 22607 Hamburg > > ######################################################################## > > To unsubscribe from the CCP4BB list, click the following link: > https://eur01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.jiscmail.ac.uk%2Fcgi-bin%2FWA-JISC.exe%3FSUBED1%3DCCP4BB%26A%3D1&data=05%7C01%7Cnicholas.pearce%40LIU.SE%7Cb01b3fe2d210435bd43108db27f4d9fc%7C913f18ec7f264c5fa816784fe9a58edd%7C0%7C0%7C638147704962813881%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=qb0fv349eLSwriyNUYdYjYw7FvjshVdZcJ%2FfUO0L2UI%3D&reserved=0 > > This message was issued to members of > https://eur01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.jiscmail.ac.uk%2FCCP4BB&data=05%7C01%7Cnicholas.pearce%40LIU.SE%7Cb01b3fe2d210435bd43108db27f4d9fc%7C913f18ec7f264c5fa816784fe9a58edd%7C0%7C0%7C638147704962813881%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=HClu5jptgnNShWKqRbtahao9debmn7YF2LDjS%2F53Ook%3D&reserved=0, > a mailing list hosted by > https://eur01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.jiscmail.ac.uk%2F&data=05%7C01%7Cnicholas.pearce%40LIU.SE%7Cb01b3fe2d210435bd43108db27f4d9fc%7C913f18ec7f264c5fa816784fe9a58edd%7C0%7C0%7C638147704962813881%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=aGjYsM25olFLtXkOd9XLOPMaLiafkInYWQgk%2BoT80YE%3D&reserved=0, > terms & conditions are available at > https://eur01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.jiscmail.ac.uk%2Fpolicyandsecurity%2F&data=05%7C01%7Cnicholas.pearce%40LIU.SE%7Cb01b3fe2d210435bd43108db27f4d9fc%7C913f18ec7f264c5fa816784fe9a58edd%7C0%7C0%7C638147704962813881%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=KftyRhu9E%2F5FSnP%2B1dly6tUZc%2Bmg5x%2FWzoubM0RAZUI%3D&reserved=0 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://eur01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.jiscmail.ac.uk%2Fcgi-bin%2FWA-JISC.exe%3FSUBED1%3DCCP4BB%26A%3D1&data=05%7C01%7Cnicholas.pearce%40LIU.SE%7Cb01b3fe2d210435bd43108db27f4d9fc%7C913f18ec7f264c5fa816784fe9a58edd%7C0%7C0%7C638147704962813881%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=qb0fv349eLSwriyNUYdYjYw7FvjshVdZcJ%2FfUO0L2UI%3D&reserved=0 This message was issued to members of https://eur01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.jiscmail.ac.uk%2FCCP4BB&data=05%7C01%7Cnicholas.pearce%40LIU.SE%7Cb01b3fe2d210435bd43108db27f4d9fc%7C913f18ec7f264c5fa816784fe9a58edd%7C0%7C0%7C638147704962813881%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=HClu5jptgnNShWKqRbtahao9debmn7YF2LDjS%2F53Ook%3D&reserved=0, a mailing list hosted by https://eur01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.jiscmail.ac.uk%2F&data=05%7C01%7Cnicholas.pearce%40LIU.SE%7Cb01b3fe2d210435bd43108db27f4d9fc%7C913f18ec7f264c5fa816784fe9a58edd%7C0%7C0%7C638147704962813881%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=aGjYsM25olFLtXkOd9XLOPMaLiafkInYWQgk%2BoT80YE%3D&reserved=0, terms & conditions are available at https://eur01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.jiscmail.ac.uk%2Fpolicyandsecurity%2F&data=05%7C01%7Cnicholas.pearce%40LIU.SE%7Cb01b3fe2d210435bd43108db27f4d9fc%7C913f18ec7f264c5fa816784fe9a58edd%7C0%7C0%7C638147704962813881%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=KftyRhu9E%2F5FSnP%2B1dly6tUZc%2Bmg5x%2FWzoubM0RAZUI%3D&reserved=0 ######################################################################## 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/
