chirality problem

From: Afshan Begum
Date: 5 January 2012 10:46

Dear Users,

I am facing difficulties to validate my structure according to PDB server. I have solved my structure and now want to submit in PDB but during validation process i have  some chirality problem specially   VAL and LEU amino acids there are total 18 amino acids which deviated from the chirality so how can i solve this problem.

Any suggestion would be highly appreciated.

 

Best Regards

AFSHAN

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From: Robbie Joosten

Hi Afshan,

Just swap the (names of) the CD and CG atoms, no need for refinement. The CCP4 dictionary allows both chiralities for LEU and VAL, so Refmac won't detect the problem. The problem is still very real to many programs so it should be fixed.

Cheers,
Robbie Joosten

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From: Paul Emsley

Hi Afshan,

This is not the solution if you are right about the problem being one of chirality (and it is if it is not and is merely an issue of nomenclature (as I suspect is the case)).  So the question is, if the problem is indeed one of nomenclature, what software (if any) described it as a chirality issue?  If it is one of ours we should fix that.

Paul

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From: Robbie Joosten

Hi Afshan,
 
I assumed, because you mentioned only VAL and LEU, that you were refering to the CB (VAL) and CG (LEU) as problematic chiral centers. Paul is right that these atoms are not chiral in a chemical sense, but they are in a computational sense because every connected atom has a unique name. The PDB is pretty strict in this sense (as it should be), but they could/should call it a nomenclature error. They could also just swap the atom names like I described and solve the problem for you. Anyway, please give a bit more details about your problem.
 
Computational chirality problem can be a serious problem for refinement: if the chirality is wrong due to swapped atom names, the chiral volume restraint will try to invert your chiral center. This can lead to malformed geometry, typically flattening of of the group. This means that a computational chirality problem can lead to a 'real' chirality problem. In Refmac, this will not happen for LEU or VAL, but it will happen for things like SO4, GOL, and a whole lot of other more interesting hetero compounds.
 
@ Paul, I don't think it will be a CCP4 program that reported the problem. Does the 'fix nomenclature problems' option in Coot also do VAL and LEU?
 
Cheers,
Robbie

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From: Katherine Sippel


Incidentally the PDB validation server will spit out similar errors if you have hydrogens on lysine side chains (also not a chiral center) should they get swapped upon regularization during refinement. It makes the chemist in me cringe a little bit.

Katherine

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From: ccp4


Wont coot fix the nomenclature issue, then you can check whether you have
a real chirality problem - eg a squashed flattened VAL..

Eleanor

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From: Paul Emsley


On 08/01/12 10:36, ccp4 wrote:

Won't coot fix the nomenclature issue, then you can check whether you have

It will indeed [1].  So Afshan need only read in the file, Press OK and then Save.

Robbie and I think that it is more likely than not that Afshan did not really have a chirality problem.

Afshan and Kim have been in touch and confirm that it is the adit validation report that describes a nomenclature error on a VAL CB as a chirality problem (rather than anything from CCP4).

Paul.


[1] well, modern ones do [2]
[2] and you can turn it off (some people find the feature annoying)

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From: Phil Evans


The problem with fixing the nomenclature "problems" in Coot is that they are back again after the next round of refinement (or at least some of them are, if they are right on the edge of an arbitrary distinction) - indeed irritating
Phil

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From: Robbie Joosten

Hi Phil,

It is annoying problem especially for Phe and Tyr which have standard
rotamers close to the critical chi angles (-90 and +90). Asp and Glu do not
have standard rotamers near critical angles, so the problem should be much
smaller (but I still get them too often). If Val, Leu and Arg problems
reoccur after refinement, then there is something seriously wrong.

Cheers,
Robbie

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From: Phil Evans

That looks to me as if the critical Chi definitions are inappropriate for Phe & Tyr!