To me this rebuttal makes perfect sense.
In a protein crystal, however, one has constraints on the edges of the "free water," such that there might be a relatively small number of solutions, and/or some solutions that are populated much more than the rest. To the extent that this be true, one would probably have non-flat water.
At a minimum, it has seemed strange to me for a while that the first shell of waters gets special treatment, but not beyond. I guess it's a simple cutoff, but I have definitely seen bona fide waters that contact only other waters and not protein.
JPK
-----Original Message-----
From: CCP4 bulletin board [mailto:[log in to unmask]] On Behalf Of Colin Nave
Sent: Sunday, November 15, 2015 6:03 AM
To: [log in to unmask]
Subject: Re: [ccp4bb] proper modeling of residues into patchy electron density
This article might be relevant regarding bulk liquid water Is ambient water inhomogeneous on the nanometer-length scale?
http://www.pnas.org/content/107/12/E44.full
Of course its relevance to the solvent within protein crystals is another matter.
Regarding modelling where there is poor (or no) interpretable electron density discernible, the option from Tassos "a. I prefer to model all atoms and let B factors go wild (PDB_REDO choice as well)"
has a potential advantage for displaying structures to non-crystallographers. If display programs can, as a default, display atoms in colours (such as green, amber and red) according to their B factor, most people, looking at a sidechain coloured red, will start to wonder about it.
Colin
From: CCP4 bulletin board [mailto:[log in to unmask]] On Behalf Of Ethan Merritt
Sent: 15 November 2015 04:34
To: ccp4bb
Subject: Re: [ccp4bb] proper modeling of residues into patchy electron density
On Saturday, 14 November 2015 11:06:15 PM Ed Pozharski wrote:
>
> Liquids have no long-range order no matter the resolution.
Tell that to the SAXS people who spend lots of beam time measuring
the water or buffer scattering in order to do background correction.
Ethan
>
>
> Happy Connecting. Sent from my Sprint Samsung Galaxy S(r) 5
>
> -------- Original message --------
> From: "Keller, Jacob"
> <[log in to unmask]<mailto:[log in to unmask]>>
> Date: 11/14/2015 10:45 PM (GMT-05:00)
> To: Ed Pozharski
> <[log in to unmask]<mailto:[log in to unmask]>>,
> [log in to unmask]<mailto:[log in to unmask]>
> Subject: RE: [ccp4bb] proper modeling of residues into patchy electron
> density
>
>
>
> Well, I was wondering whether the uniform bulk solvent density assumption might break down given sufficient data.
>
> JPK
>
>
>
> From: CCP4 bulletin board [mailto:[log in to unmask]]
> On Behalf Of Ed Pozharski
>
> Sent: Saturday, November 14, 2015 9:33 PM
>
> To: [log in to unmask]<mailto:[log in to unmask]>
>
> Subject: Re: [ccp4bb] proper modeling of residues into patchy electron
> density
>
>
>
>
> No - a set of discrete water molecules would approach a uniform
> density as you elevate B-factors to infinity. But it would never be
> exactly identical to it, still having hills and valleys. Naturally,
> in practical terms such approach would
> be problematic because of potential model bias.
>
>
>
>
>
>
>
>
>
>
>
>
> Happy Connecting. Sent from my Sprint Samsung Galaxy S(r) 5
>
>
>
>
>
>
> -------- Original message --------
>
> From: James Holton <[log in to unmask]<mailto:[log in to unmask]>>
>
> Date: 11/14/2015 7:27 PM (GMT-05:00)
>
> To: Ed Pozharski
> <[log in to unmask]<mailto:[log in to unmask]>>,
> [log in to unmask]<mailto:[log in to unmask]>
>
> Subject: Re: [ccp4bb] proper modeling of residues into patchy electron
> density
>
>
>
>
> Isn't that exactly what the bulk solvent correction is? Except that the B factor and occupancy of all the disordered water "atoms" are constrained to be the same?
>
>
>
> -James Holton
>
> MAD Scientist
>
>
>
> On 11/14/2015 4:23 PM, Ed Pozharski wrote:
>
>
>
> This is a bit confusing. Don't you already know the "location" from backbone coordinates?
>
>
>
>
>
> I still would like to hear exactly how placing atoms to where no
> discernible density peak exists is improving a crystallographic model.
> I also know waters are there in large numbers, should I flood the bulk
> solvent area with discrete waters
> and state that B-factors will take care of "it"?
>
>
>
>
>
> Cheers,
>
>
>
>
>
> Ed.
>
>
>
>
>
>
>
>
>
>
>
>
> Happy Connecting. Sent from my Sprint Samsung Galaxy S(r) 5
>
>
>
>
>
>
> -------- Original message --------
>
> From: Quyen Hoang <[log in to unmask]<mailto:[log in to unmask]>>
>
> Date: 11/14/2015 6:23 PM (GMT-05:00)
>
> To: [log in to unmask]<mailto:[log in to unmask]>
>
> Subject: Re: [ccp4bb] proper modeling of residues into patchy electron
> density
>
>
>
> Let's see if we can settle this. Ed might remember where I stood, but my view had changed a bit.
>
> 1. Delete atoms of a side-chain for which no density is visible if one is using density to find out what the residue looks like.
>
> 2. Model a complete residue even when density is missing for a side-chain atom if one is using the density to find the location of the residue.
>
>
>
> Can we settle with this?
>
>
>
> Cheers,
>
> Quyen
>
>
>
>
>
> On Nov 14, 2015, at 5:40 PM, Ed Pozharski
> <[log in to unmask]<mailto:[log in to unmask]>> wrote:
>
>
>
> > On 11/14/2015 04:36 PM, Artem Evdokimov wrote:
>
> >>
>
> >> I would agree with both sides, since absence of evidence is not evidence of ansence.
>
> >>
>
> > Well, that's agnostic :)
>
> >
>
> > Just a comment - omitting side chain atoms from the model does not
> > assert that they are somehow missing from the chemical structure one
> > is modeling. It means that their spatial distribution cannot be
> > adequately approximated from experimental data via simple
> 3D gaussian. So when I am excluding atoms from disordered side chains, I am not saying that an X-ray fairy has cut off covalent bonds with a tiny magic chainsaw. I am just saying I don't have sufficient experimental evidence to locate these atoms.
>
> >
>
> > Cheers,
>
> >
>
> > Ed
>
>
>
>
--
mail: Biomolecular Structure Center, K-428 Health Sciences Bldg
MS 357742, University of Washington, Seattle 98195-7742
--
This e-mail and any attachments may contain confidential, copyright and or privileged material, and are for the use of the intended addressee only. If you are not the intended addressee or an authorised recipient of the addressee please notify us of receipt by returning the e-mail and do not use, copy, retain, distribute or disclose the information in or attached to the e-mail.
Any opinions expressed within this e-mail are those of the individual and not necessarily of Diamond Light Source Ltd.
Diamond Light Source Ltd. cannot guarantee that this e-mail or any attachments are free from viruses and we cannot accept liability for any damage which you may sustain as a result of software viruses which may be transmitted in or with the message.
Diamond Light Source Limited (company no. 4375679). Registered in England and Wales with its registered office at Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom
|