[phenixbb] Dual conformation on symmetry axis

[Andreas Forster]

Tim,

with MD simulation I get the right answer no matter where I model the side
chain.  As long as it is there, it will be subject to the force field and
will move into the right position.  If the position is indeed the right
one, it will be same no matter where the side chain started out, as long as
the simulation reached equilibrium.  If the side chain is disordered in the
structure, MD will also show that by having the side chain float around
aimlessly - but only if it's there in the first place.

For surface charge plots, I'd argue that the exact position of the charged
group doesn't matter either because you don't expect atomic resolution
anyway but blue and red patches.  However, if the charged residues (which
are often flexible) aren't there, you'll just get gray and wonder why the
protein is soluble at all.  (Actually, you won't.  APBS will fail to
parametrize the erroneous structure because there are residues with missing
atoms.)

That's why it is critical to model ALL side chains for which there is main
chain.

Best


Andreas


On Fri, Feb 5, 2016 at 10:13 AM, Tim Gruene <tim.gruene at psi.ch> wrote:

> Dear Andreas,
>
> if you use a side chain in an arbitrary orientation, you may get some
> results
> for surface charge plots or molecular dynamics simulation. However, do they
> correspond to the experimental data?
>
> At least when the side chain is missing, it is much easier, especially for
> these non-crystallographic applications (or rather crysallographically non-
> educated users), to realise they are missing and that appropriate care
> should
> be taken in interpreting the model.
>
> Your email just underlines how important it is to NOT model side chains
> when I
> don't see density for them: I don't want my models to be misinterpreted,
> and I
> want its users to be made aware of its limits.
>
> Best,
> Tim
>
> On Friday, February 05, 2016 10:06:10 AM Andreas Forster wrote:
> > Dear Jan and Tim,
> >
> > two little comments.
> >
> > If Arg in A clashes with Arg in A* and Arg has multiple conformations,
> > couldn't you just fix the occupancy of the clashing conformation to 0.5?
> > The two will add up to one, and there won't be a clash left.  The
> remaining
> > 0.5 occupancy would be in the other one or more conformations?
> >
> > I agree with Tim regarding artefacts on symmetry axes.  However, please
> > don't remove side chains that are there.  I know this is a contentious
> > subject and has been discussed ad nauseam on the CCP4 mailing list, with
> no
> > consensus emerging.  To me it is a no-brainer that if a side chain is
> > present in the protein, it should be part of the model as well, whether
> at
> > zero occupancy or with mental B values (my preferred way) - though I
> > realize that far from everyone finds this argument convincing.  However,
> > for surface charge plots and for molecular dynamics simulations, complete
> > side chains are essential for correct parametrization.
> >
> > All best.
> >
> >
> > Andreas
> >
> > On Fri, Feb 5, 2016 at 9:35 AM, Tim Gruene <tim.gruene at psi.ch> wrote:
> > > Dear Jan,
> > >
> > > density on symmetry elements usually displays artefacts and is
> difficult
> > > to
> > > interpret. If A clashes with A*, this is a real clash and you should
> not
> > > ask
> > > for this clash to be ignored.
> > >
> > > Is this Arg biologically relevant? Otherwise, especially given the
> medium
> > > resolution, you probably create a better model by removing the side
> chain,
> > > even if that leaves difference density.
> > >
> > > Best,
> > > Tim
> > >
> > > On Thursday, February 04, 2016 01:38:11 PM Jan Abendroth wrote:
> > > > Hi all,
> > > > I am running into the following problem during the refinement of a
> > > > rather
> > > > small structure at 2.15Å resolution:
> > > >
> > > > An Arg side chain is located very close to a crystallographic 2-fold.
> > >
> > > There
> > >
> > > > is good evidence that the side chain has two conformations. However,
> > > > because of the 2-fold, conformer A overlaps with its symmetry mate
> A*,
> > > > as
> > > > does conformer B. Phenix wants to avoid this 'clash' and moves A and
> A*
> > >
> > > out
> > >
> > > > of the density, same for B and B*.
> > > >
> > > > Is there a way to avoid this without reducing the symmetry? In the
> real
> > > > crystal, of course the two side chains are agnostic as to if they are
> > > > called A or B and will avoid one another ...
> > > >
> > > > Thanks!
> > > > Jan
> > > >
> > > > --
> > > > Jan Abendroth
> > > > Emerald Biostructures
> > > > Seattle / Bainbridge Island, WA, USA
> > > > home: Jan.Abendroth_at_gmail.com
> > > > work: JAbendroth_at_embios.com
> > > > http://www.emeraldbiostructures.com
> > >
> > > --
> > > --
> > > Paul Scherrer Institut
> > > Dr. Tim Gruene
> > > - persoenlich -
> > > OFLC/102
> > > CH-5232 Villigen PSI
> > > phone: +41 (0)56 310 5297
> > >
> > > GPG Key ID = A46BEE1A
> > >
> > >
> > > _______________________________________________
> > > phenixbb mailing list
> > > phenixbb at phenix-online.org
> > > http://phenix-online.org/mailman/listinfo/phenixbb
> > > Unsubscribe: phenixbb-leave at phenix-online.org
> --
> --
> Paul Scherrer Institut
> Dr. Tim Gruene
> - persoenlich -
> OFLC/102
> CH-5232 Villigen PSI
> phone: +41 (0)56 310 5297
>
> GPG Key ID = A46BEE1A
>
>
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://phenix-online.org/pipermail/phenixbb/attachments/20160205/c454fd9c/attachment.htm>