On 7/13/2012 1:58 AM, Tim Gruene wrote:
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Dear all,
I am surprised by the discussion about "chiraliy" of an utterly
centrosymmetric molecule. Shouldn't the four Oxygen atoms be at least
from a QM point-of-view to indistinguishable? What reason is there to
maintain a certain 'order' in the human-induced numbering scheme?
There are good reasons for maintaining "order" in this human-induced
numbering scheme. A common operation is to superimpose two molecules
and calculate the rmsd of the positional differences. This calculation
is not useful when the Val CG1 and CG2 are swapped in one molecule relative
to the other. Suddenly you have, maybe a handful, of atoms that differ
in position by about 3.5 A when most of us would consider this to be
nonsense. We want the rmsd between equivalent atoms regardless of the
"human-induced numbering scheme". There are two ways this can come about.
1) The overlay program could swap the labels on one to match the other or
2) The labels can be defined to be consistent from the start.
Neither 1) or 2) are objectively better in any absolute sense. The
Powers that Be, however, have decided that for Val, Leu, Phe, Tyr, and
the PO2 in DNA, RNA, and many co-enzymes models should be adjusted to
conform to a standard. If we are doing this for these groups in order
to make comparison of models simpler, why stop there? If we say there
are standards for some groups but not others we have the worst of both
worlds - We have to both modify models and write complicated comparison
programs.
The failure of comparison programs to correct for labeling differences
is generally a silent error - A handful of 3.5 A differences mixed into
thousands of very small differences will not likely cause an increase in
the rmsd that would be noticed. Only if the individual differences are
plotted, or the biggest differences are listed will the user notice the
problem. Silent errors are the worst errors since they are the most
likely to make it all the way to publication.
As I see it, the problem here lies in the program that created the
original poster's SO4 group. If it had matched the convention now present
in the CCP4 cif there would be none of these problems. That program
should be tracked down and updated.
The problem of labeling groups that have symmetry along a rotatable
torsion angle is a persistent problem that, I'm afraid, has no permanent
solution other than CONSTANT VIGILANCE. I see that the newer versions
of Coot have taken up this burden, at least for Phe and Tyr. (I guess
we need a picture of a coot with one big roving eye.)
Since we are already unambiguously defining the labeling for a number
of the groups we use, I think it is up to you to justify why this group
should be treated differently.
Dale Tronrud
P.S. On a only slightly off topic note - I'm quite afraid of using "both"
as the definition for chirality. I've noticed that this keyword is used
as an excuse to not figure out what the real chirality of an atom is and
as a result people build models with bad chiral centers that are not flagged
by their software (another silent error that makes it to publication.) The
PDB is littered with cofactors and ligands that have inverted chiral centers
(Even centers that Pasteur would approve). I would prefer that "both"
was not a legal value and researchers would be required to think about
chirality.
Cheers,
Tim
On 07/13/12 00:22, Dale Tronrud wrote:
While this change has made your symptom go away it is stretching it
a bit to call this a "fix". You have not corrected the root
problem that the names you have given your atoms do not match the
convention which is being applied for SO4 groups. Changing the cif
means that you don't have to worry about it, but people who study
such details will be forced to deal with the incorrect labels of
your model in the future.
Wouldn't it just be easier to swap the names of two oxygen atoms in
each SO4, leaving the cif alone? Your difficulties will go away
and people using your model in the future will also have a simpler
life.
This labeling problem is not new. The fight to standardize the
labeling of the methyl groups in Valine and Leucine was raging in
the 1980's. Standardizing the labels on the PO4 groups in DNA/RNA
was much more recent. It helps everyone when you know you can
overlay two models and have a logical solution without a "rotation
matrix" with a determinate of -1.
Besides, you will continue to be bitten by this problem as you use
other programs, until you actually swap some labels.
Dale Tronrud
On 07/12/12 15:00, Joel Tyndall wrote:
Hi all,
Thanks very much to all who responded so quickly. The fix is a
one liner in the SO4.cif file (last line)
SO4 chir_01 S O1 O2 O3 both
which I believe is now in the 6.3.0 release.
Interestingly the chirality parameters were not in the SO4.cif
file in 6.1.3 but then appeared in 6.2.0.
Once again I'm very happy to get to the bottom of this and get it
fixed. I do wonder if it had become over parametrised.
Cheers
Joel
-----Original Message----- From: CCP4 bulletin board
[mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Robbie Joosten Sent:
Thursday, 12 July 2012 12:16 a.m. To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] Chiral volume outliers SO4
Hi Ian,
@Ian: You'd be surprised how well Refmac can flatten sulfates
if you have a chiral volume outlier (see Figure 1d in Acta
Cryst. D68: 484-496
(2012)). But this is only because the 'negative' volume sign
was erroneously used
in
the chiral restraint instead of 'both' (or better still IMO no
chiral
restraint at
all), right? If so I don't find it surprising at all that
Refmac tried to
flip the
sulphate and ended up flattening it. Seems to be a good
illustration of the GIGO (garbage in - garbage out) principle.
Just because the garbage input in this case is in the
official
CCP4 distribution and not (as is of course more commonly the
case) perpetrated by the user doesn't make it any less
garbage.
The problem is that in the creation of chiral volume targets
chemically equivalent (groups of) atoms are not recognized as
such. So any new or recreated restraint files will have either
'positiv' or 'negativ' and the problem starts all over again.
That is why it is better to stay consistent and choose one
chirality (the same one as in the 'ideal' coordinates in the PDB
ligand descriptions). This will also make it easier compare
ligands after aligning them (this applies to ligands more complex
than sulfate). Obviously, users should not be forced to deal with
these things. Programs like Refmac and COOT should fix chiral
volume inversions for the user, because it is only relevant
inside the computer. That is the idea of chiron, just fix these
'problems' automatically by swapping equivalent atoms whenever
Refmac gives a chiral volume inversion warning. It should make
life a bit easier.
The point I was making is that in this and similar cases you
don't need a
chiral
restraint at all: surely 4 bond lengths and 6 bond angles
define the
chiral
volume pretty well already? Or are there cases where without a
chiral restraint the refinement still tries to flip the
chirality (I would fine
that hard to
believe).
I agree with you for sulfate, and also for phosphate ;). I don't
know what happens in other compounds at poor resolution, when
bond and angle targets (and their SDs) are not equivalent. I
guess that some angle might 'give way' before others. That is
something that should be tested. I have a growing list of chiral
centers that have this problem if you are interested.
Cheers, Robbie
- --
- --
Dr Tim Gruene
Institut fuer anorganische Chemie
Tammannstr. 4
D-37077 Goettingen
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