The most pertinent question is, of course, what is the average frequency of the disordered chain controversy flareup. Once we figure that out, some profound mysteries of the Universe will reveal themselves. I am betting it's a simple combination of the solar cycle, inflation adjusted price of a bag of roasted chestnuts at Heinzels Wintermärchen and certainly the time elapsed since the most recent cicada emergence in Montgomery County, Maryland. I am still working on the fudge factors, but maybe I should just ask a neural network.
Aha, here is the (non)-answer to "What should I do about disordered sidechains" Disordered sidechains can be a common issue in protein structures, > particularly in regions that are flexible or have low electron density. One > approach is to manually adjust the position of the sidechain using software > tools such as Coot or PyMOL. However, if the resolution of the protein > structure is low or the disorder is extensive, it may be difficult to > accurately position the sidechain. In such cases, it may be necessary to > consider alternative approaches such as mutagenesis, site-directed labeling > or multiple conformer modeling. The specific approach would depend on the > particular protein structure being studied and the goals of the research > project. Joking aside, here is what I learned from the vigorous dead horse beatings in the past. - Some people like keeping adding invisible atoms to side chains and letting B factors sort it out, Caedite eos. Novit enim Dominus qui sunt eius. - Some people like to remove invisible atoms. These weirdos claim that all atoms should be treated equally, and that adding a bunch of arginine atoms is not different from completing the his-tag or adding hydrogens at medium resolution. They point out that adding disordered side chains (marginally) increases statistical error on the rest of the well defined structure ( https://tinyurl.com/yvz73ak2) and refer to the practice as orwellian. Snobs, basically. - A small minority assigns zero occupancy to disordered atoms. I admire them as they have gone beyond agnosticism. Let me give you coordinates for the atom, they say. Let me then tell you that atoms are never there and thus have zero occupancy at that position. Meaningless, you say? Well, so is your existence and Santa Claus is your parents. Now that my telomeres are a few hundred units shorter than they were last time I whipped myself up into a frenzy over disordered side chains, I would summarize my views this way. *People are free to choose how to interpret experimental data that they themselves obtained. * *Published structures are reported to the PDB, and if someone doesn't like what I did to my arginines - well, interpret it your own way, I am not stopping you. * Also, this (with full appreciation of the formal ccp4bb focus on computational crystallography - but come on, you are not here for the maximum likelihood formalism) *I am yet to see an example of when different modeling of a disordered side chain 30 angstroms away from the area where actual molecular biology happens has changed conclusions derived from protein structure in question.* Special thanks to Adrian Goldman for changing my attitude on this specific point years ago. Cheers. --- I don't know why the sacrifice didn't work. The science seemed so solid. Julien XIII, Lord of the Lemurs On Thu, Mar 9, 2023 at 8:26 PM Rhys Grinter < 000022087c81e8c6-dmarc-requ...@jiscmail.ac.uk> wrote: > 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 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/
