Vaheh, I think coordinates are no different from B factors, occupancies, f', or f'' in this respect. Coordinates can play their "trash bin" role by adjusting to the noise at the expense of violated geometry (bonds, angles, planes, torsions, etc.). As I mentioned in my previous email, their trash bin capacity is much smaller (but definitely not zero!) because the number and strength (confidence) of geometry restraints are much greater than those of ADP restraints.
I agree that all refined parameters share this trash bin capacity, but to varying degrees. Isn't this essentially what we call the error on the refined parameter? All refined parameters have their error bars, which we have referred to as the "trash bin" in this thread. Pavel On Tue, Jul 30, 2024 at 10:09 AM Oganesyan, Vaheh < vaheh.oganes...@astrazeneca.com> wrote: > Your point is taken, Pavel. However, despite resolution, you define > coordinate of the atom as a geometric point with no width. Although > coordinates are “refineable”, they have no capacity for “trash”. Their > “trash” still goes into B-factor “trash bin”. At least this is how I see it. > > > > Thank you. > > > > *Vaheh Oganesyan, Ph.D.* > > *R&D* *| Biologics Engineering* > > One Medimmune Way, Gaithersburg, MD 20878 > > T: 301-398-5851 > > *vaheh.oganes...@astrazeneca.com <oganesy...@medimmune.com>* > > > > > > > > *From:* Pavel Afonine <pafon...@gmail.com> > *Sent:* Tuesday, July 30, 2024 11:45 AM > *To:* Oganesyan, Vaheh <vaheh.oganes...@astrazeneca.com> > *Cc:* CCP4BB@jiscmail.ac.uk > *Subject:* Re: [ccp4bb] How high a B factor is too high to assume a loop > is in place, in the AlphaFold era? > > > > From this perspective, all refinable atomic model parameters can be viewed > as trash bins, with the size of these bins being proportional to the amount > of prior information (restraints) imposed on these parameters. For example, > coordinates have the most restraints and thus are the smallest trash bins, > while B factors have the least restraints and thus are one of the largest > bins. > > Pavel > > > > > > On Tue, Jul 30, 2024 at 8:25 AM Oganesyan, Vaheh < > vaheh.oganes...@astrazeneca.com> wrote: > > Early in my Crystallography life I was postdoc with Robert Huber in > Munich. We had those gatherings once a week when in very informal way we > can ask and answer questions. I remember my question about B factors: how > is it possible to have high resolution structure and average B-factor of > 100A2. I think it was Robert or Albrecht Messerschmidt who told that > B-factor is a “trash can” that describes not only loosely positioned atoms > but also all other problems that either you created during processing, > harvesting or crystal had from the beginning. > > > > *Vaheh Oganesyan, Ph.D.* > > *R&D **| Biologics Engineering* > > One Medimmune Way, Gaithersburg, MD 20878 > > T: 301-398-5851 > > *vaheh.oganes...@astrazeneca.com <oganesy...@medimmune.com>* > > > > > > > > *From:* CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> *On Behalf Of *James > Holton > *Sent:* Tuesday, July 30, 2024 10:35 AM > *To:* CCP4BB@JISCMAIL.AC.UK > *Subject:* Re: [ccp4bb] How high a B factor is too high to assume a loop > is in place, in the AlphaFold era? > > > > How high B factors can go depends on the refinement program you are > using. > > In fact, my impression is that the division between the "let the B factors > blow up" and "delete the unseen" camps is correlated to their preferred > refinement program. You see, phenix.refine is relatively aggressive with B > factor refinement, and will allow "missing" atoms to attain very high B > factors. Refmac, on the other hand, has restraints that try to make B > factor distributions look like those found in the PDB, and so tends to keep > nearby B factors similar. As a result, you may get "red density" for > disordered regions from refmac, inviting you to delete the offending atoms, > but not from phenix, which will raise the B factor until the density fits. > > Then there are programs like VagaBond that don't formally have B factors, > but rather let an ensemble of chains spread out in the loopy regions you > are concerned about. This might be the way to go? > > You can also do ensemble refinement in the latest Amber. That is, you run > an MD simulation of a unit cell (or more) and gradually increase structure > factor restraints. This would probably result in the "fan" of loops you > have in mind? > > -James Holton > MAD Scientist > > On 7/28/2024 8:13 AM, Javier Gonzalez wrote: > > Dear CCP4bb, > > > > I'm refining the ~3A crystal structure of a big protein, largely composed > of alpha helices connected by poorly-resolved loops. > > In the old pre-AlphaFold (AF) days I used to simply remove those > loops/regions with too high B factors, because there was little to none > density at 1 sigma in a 2Fo-Fc map. > > However, considering that the quality of a readily-computable AF model is > comparable to a 3A experimental structure, and that the UniProt database is > flooded with noodle-like AF models, I was considering depositing a combined > model in the PDB. > > Once R/Rfree reach a minimum for the model truncated in poorly resolved > loops, I would calculate an augmented model with AF calculated missing > regions (provided they have an acceptable pLDDT value), assign them zero > occupancy, and run only one cycle of refinement to calculate the formal > refinement statistics. > > Would that be acceptable? Has anyone tried a similar approach? > > I'd rather do that instead of depositing a counterintuitive model with > truncated regions that few people would find useful!! > > > > Thank you for your comments, > > > > Javier > > > -- > > Dr. Javier M. González > Instituto de Bionanotecnología del NOA (INBIONATEC-CONICET) > Universidad Nacional de Santiago del Estero (UNSE) > RN9, Km 1125. Villa El Zanjón. (G4206XCP) > Santiago del Estero. Argentina > > Tel: +54-(0385)-4238352 > > Email <bio...@gmail.com> Twitter <https://twitter.com/_biojmg> > > > > > ------------------------------ > > 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 > > ######################################################################## 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/
