Dear Jacob, What do we gain? As Dale pointed out, we are already abusing either occupancy, B-factor or delete the side chain to compensate for our inability to tell the user that the side chain is disordered. With your proposal, we would fudge both occupancy and B-factor, which in my eyes is even worse as fudging just one of the two.
Also, who should decide on the magic number: the all-knowing gurus at the protein data bank? Maybe we should really start using cif files, which allow to specify coordinate uncertainties. Best regards, Herman -----Original Message----- From: Jacob Keller [mailto:[email protected]] Sent: Thursday, March 31, 2011 4:43 PM To: Schreuder, Herman R&D/DE Cc: [email protected] Subject: Re: [ccp4bb] what to do with disordered side chains Why not have the "b-factors take care of it" until some magic cutoff number? When they reach the cutoff, two things happen: 1. Occupancies are set to zero for those side chains, to represent our lack of ability to model the region, 2. B-factors are set to exactly 500, as a "flag" allowing casual b-factor-savvy users to identify suspicious regions, since they will probably not see occupancies, but *will* see b-factors. Therefore, all 0-occupancy atoms will automatically have b-factors = 500. I believe it is true that if the occupancies are zero, the b-factors are totally irrelevant for all calculations? Doesn't this satisfy both parties? Jacob On Thu, Mar 31, 2011 at 9:22 AM, <[email protected]> wrote: > Dear Quyen, > I am afraid you won't get any better answers than you got so far. > There is no holy bible telling you what to do with disordered side > chains. I fully agree with James that you should try to get the best > possible model, which best explains your data and that will be your decision. > Here are my 2 cents: > > -If you see alternative positions, you have to build them. > -If you do not see alternative positions, I would not replace one > fantasy (some call it most likely) orientation with 2 or 3 fantasy > orientations. > -I personally belong to the "let the B-factors take care of it" camp, > but that is my personal opinion. Leaving side chains out could lead to > misinterpretations by slightly less savy users of our data, especially > when charge distributions are being studied. Besides, we know (almost) > for sure that the side chain is there, it is only disordered and as we > just learned, even slightly less savy users know what flaming red side > chains mean. Even if they may not be mathematically entirely correct, > huge B-factors clearly indicate that there is disorder involved. > -I would not let occupancies take up the slack since even very savy > users have never heard of them and again, the side chain is fully > occupied, only disordered. Of course if you build alternate positions, > you have to divede the occupancies amongst them. > > Best, > Herman > > ________________________________ > From: CCP4 bulletin board [mailto:[email protected]] On Behalf Of > Quyen Hoang > Sent: Thursday, March 31, 2011 3:55 PM > To: [email protected] > Subject: Re: [ccp4bb] what to do with disordered side chains > > We are getting off topic a little bit. > Original topic: is it better to not build disordered sidechains or > build them and let B-factors take care of it? > Ed's poll got almost a 50:50 split. > Question still unanswered. > Second topic introduced by Pavel: "Your B-factors are valid within a > harmonic (small) approximation of atomic vibrations. Larger scale > motions you are talking about go beyond the harmonic approximation, > and using the B-factor to model them is abusing the corresponding > mathematical model." > And that these large scale motions (disorders) are better represented > by "alternative conformations and associated with them occupancies". > My question is, how many people here do this? > If you're currently doing what Pavel suggested here, how do you decide > where to keep the upper limit of B-factors and what the occupancies > are for each atom (data with resolution of 2.0A or worse)? I mean, do > you cap the B-factor at a reasonable number to represent natural > atomic vibrations (which is very small as Pavel pointed out) and then > let the occupancies pick up the slack? More importantly, what is your reason > for doing this? > Cheers and thanks for your contribution, Quyen > > On Mar 30, 2011, at 5:20 PM, Pavel Afonine wrote: > > Mark, > alternative conformations and associated with them occupancies are to > describe the larger scale disorder (the one that goes beyond the > B-factor's capability to cope with). > Multi-model PDB files is another option. > Best, > Pavel. > > > On Wed, Mar 30, 2011 at 2:15 PM, VAN RAAIJ , MARK JOHAN > <[email protected]> wrote: >> >> yet, apart from (and additionally to) modelling two conformations of >> the side-chain, the B-factor is the only tool we have (now). >> Quoting Pavel Afonine: >> >> > Hi Quyen, >> > >> > >> > (...) And if B-factor is an estimate of thermo-motion (or static >> > disorder), >> >> then would it not be reasonable to accept that building the >> >> side-chain and let B-factor sky rocket might reflect reality more >> >> so than not building it? >> >> >> > >> > NO. Your B-factors are valid within a harmonic (small) >> > approximation of atomic vibrations. Larger scale motions you are >> > talking about go beyond the harmonic approximation, and using the >> > B-factor to model them is abusing the corresponding mathematical >> > model. >> > http://www.phenix-online.org/newsletter/CCN_2010_07.pdf >> > >> > Pavel. >> > >> >> Mark J van Raaij >> Laboratorio M-4 >> Dpto de Estructura de Macromoléculas >> Centro Nacional de Biotecnología - CSIC c/Darwin 3, Campus >> Cantoblanco >> 28049 Madrid >> tel. 91 585 4616 >> email: [email protected] > > > -- ******************************************* Jacob Pearson Keller Northwestern University Medical Scientist Training Program cel: 773.608.9185 email: [email protected] *******************************************
