Good afternoon both,
there is also the issue of inconsistency of presentation.
For example, Lysine, that is L-Lysine (LYS) is protonated on the side
chain nitrogen (NZ), whiles as D-lysine (DLY) is not.
i.e. you have NZ(HZ1, HZ2) for DLY, and NZ(HZ1, HZ2, HZ3) for LYS
Miri
On Wed, 2015-06-24 at 13:35 +0100, Ian Tickle wrote:
> Hi Ben
>
>
> From discussions we have had with PDBe they consider tautomers to be
> different compounds (just as stereoisomers would be considered to be
> different compounds), since they require different restraint
> dictionaries, so each tautomer that was observed would require a
> unique 3-lettter code. Of course you still have to have evidence
> (e.g. from the H-bonding pattern) that what you are really seeing are
> different tautomers, but that's a different question.
>
>
> Cheers
>
>
> -- Ian
>
>
>
> On 24 June 2015 at 12:50, Ben Bax <[log in to unmask]> wrote:
> Another major problem with the PDB is that it does not seem to
> believe in the existence of different tautomers or protonation
> states.
>
> For example the ATP analogue AMPPNP can have the nitrogen
> between the beta and gamma phosphates protonated (-P-NH-P) or
> unprotonated (P-N=P), and there are well documented examples
> of both tautomers in the PDB (NH being a hydrogen bond donor
> and N a hydrogen bond acceptor).
> If you look in the CSD you can see that the protonation state
> of the nitrogen changes the geometry of the P-N-P bond.
>
> However, as I understand it, the PDB considers all tautomeric
> (and protonated) forms of AMPPNP the same. When I tried to
> deposit a specific AMPPNP tautomer in 2013, they would not
> accept it. The PDB also seems to believe, as I understand it,
> that the overall charge on AMPPNP is zero and that the
> phosphates do not carry negative charge.
>
>
> Ben Bax
> Senior Scientific Investigator
> BioMolecular Sciences UK
> RD Platform Technology & Science
>
> GSK
> Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1
> 2NY, UK
> Email [log in to unmask]
> Mobile +44 (0) 7912 600604
> Tel +44 (0) 1438 55 1156
>
> gsk.com | Twitter | YouTube | Facebook | Flickr
>
>
>
>
>
>
>
>
>
>
>
> -----Original Message-----
> From: CCP4 bulletin board [mailto:[log in to unmask]] On
> Behalf Of Martyn Symmons
> Sent: 22 June 2015 23:39
> To: [log in to unmask]
> Subject: Re: [ccp4bb] [Fwd: Re: [ccp4bb] FW: New ligand
> 3-letter code (help-7071)]
>
> Well the problem is there is a lot more to a ligand than PDB
> coordinates - little things like bond orders... In addition
> people can publish ligands with atoms for which they have no
> density - so zero-occupancy is allowed too. So who should get
> priority - the group who publishes a ligand first, or the ones
> who actually have density for all the atoms?
>
> These sorts of complications mean we all benefit from
> peer-review of the structure - that is why we put things on
> hold. And authors should have a chance to change their ligand
> definition based on reviewers'
> comments - just as they are allowed to improve the PDB
> coordinates. So it is a worry for them that the PDB might
> 'publish' the ligand aspect of their work before they have
> completed the peer-review process.
>
> Maybe you don't believe is peer-review - in reply to which I'd
> paraphrase what people say about democracy - it's pretty bad
> but better than the alternatives.
>
> But to return to the point I made: what really is the problem
> with maintaining and modifying _separate_ definitions with
> authors'
> _separate_ deposited coordinates (and bond orders) while
> structures are on hold and being reviewed? Journals manage to
> keep all those submitted papers separate in their databases.
>
> cheers
> M.
>
> On Mon, Jun 22, 2015 at 3:12 AM, Edward A. Berry
> <[log in to unmask]> wrote:
> >> I can't imagine a journal doing that can you? When I
> work on my
> >> supplementary material in a paper I don't expect that the
> journal
> >> will take a bit out and publish it separately to support
> the work of
> >> my competitors. Not out of spite that I was beaten - but
> because I
> >> don't want to take the responsibility for checking their
> science for them!
> >
> >
> > I don't see the problem here. What about the dozens of
> authors who
> > will benefit from using your ligand in their structure
> _after_ your
> > structure comes out? You don't take responsibility for
> checking their
> > science. Every author gets a copy of his final structure to
> check
> > before it is released and each is responsible for his own.
> > The only difference here is whether the competitor got to
> use it
> > first, (which might sting a bit) or only after you had
> already made it
> > your own with the first structure.
> >
> > I guess the ligand database is the responsibility of the
> pdb, but they
> > depend on first depositors to help set up each ligand, so it
> is not
> > surprising if the type model has coordinates from the first
> > depositor's structure (although it would be convenient if
> they were
> > all moved to c.o.m. at 0,0,0). When another group publishes
> a
> > structure with the ligand, they will not be publishing the
> first
> > depositor's coordinates because the ligand will be moved to
> its
> > position in their structure and refined against their data,
> probably
> > with somewhat different restraints.
> >
> > If the ligand is a top secret novel drug lead that your
> company is
> > developing I guess it would come as a shock to find someone
> else has
> > already deposited it, and it might be good to hasten not
> the
> > publication but protecting of the compound with a patent!
> >
> > Although Miriam says a new 3-letter code is generated when
> no match is
> > found, I believe the depositor's code will be used if it is
> available,
> > at least one of mine was last year, so there is some use for
> Nigel's
> > utility if you want to stamp your new compound with a
> rememberable name.
> >
> > eab
> >
> >
> > On 06/21/2015 06:33 PM, Martyn Symmons wrote:
> >>
> >> Miri raises important points about issues in the PDB
> Chemical
> >> Component Dictionary - I think part of the problem is that
> this is
> >> published completely separately from the actual PDB - so
> for example
> >> I don't think we have an archive of the CCD for comparison
> alongside
> >> the PDB snapshots? This makes it difficult to follow the
> convoluted
> >> track of particular ligands through the PDB's many,many
> changes to
> >> small molecule definitions.
> >>
> >> But following discussion with other contributors offline I
> want to
> >> make it clear what is my understanding of the ZA3
> (2Y2I /2Y59) case:
> >>
> >> I am clear there was no unethical behaviour by either group
> in the
> >> course of their work on these structures and the
> publication of them.
> >>
> >> The problem I am highlighting is that the PDB don't
> understand
> >> publishing ethics - what happened in ZA3 was that they
> published a
> >> little bit of one group's work to support the work of
> someone who was
> >> scooping them!
> >>
> >> I can't imagine a journal doing that can you? When I
> work on my
> >> supplementary material in a paper I don't expect that the
> journal
> >> will take a bit out and publish it separately to support
> the work of
> >> my competitors. Not out of spite that I was beaten - but
> because I
> >> don't want to take the responsibility for checking their
> science for them!
> >>
> >> All the best
> >> Martyn
> >>
> >> Cambridge
> >>
> >> On Sun, Jun 21, 2015 at 7:01 PM, Miri Hirshberg
> >> <[log in to unmask]> wrote:
> >>>
> >>> Sun., June 21st 2015
> >>>
> >>> Good evening,
> >>>
> >>> adding several general points to the thread.
> >>>
> >>> (1) Fundamentally PDB unlike other chemical databases
> insists that
> >>> all equal structures should have the same 3-letter code
> and the same
> >>> atom names - obviously for amino acids and say ATP.
> >>>
> >>> (1.1) Needless to say there are endless examples in the
> PDB of two
> >>> ligands differ by let say one hydroxyl group, where
> equivalent atoms
> >>> in the two ligands having totally different names.
> >>>
> >>> (2) When a structure is deposited with a ligand, the
> ligand is first
> >>> compared against PDB chem_comp database (CCD) and against
> the
> >>> on-hold chem_comp (CCD) (naturally the latter is not
> publicly
> >>> available), and only if no-match can be found a new
> three-letter
> >>> code is generated and assigned.
> >>>
> >>> If not, then this is a mistake in annotation and should
> not happen.
> >>>
> >>> (3) Exception to the above take several different
> flavours. This
> >>> include:
> >>>
> >>> (3.1) When the same ligand is described in PDB as a
> 3-letters-code
> >>> and as well as a combination of two different
> 3-letters-code ligands.
> >>> An example out of many is phosphoserine. The 3-letter-code
> in PDB
> >>> CCD is SEP which is used in 704 PDB entries (RCSB
> counting
> >>> 21-June-2015). But in the PDB entry 3uw2 the phosphoserine
> 109A is
> >>> described as a combination of SER and the inorganic
> phosphate PO4 !!!
> >>> (a side point: note the inorganic PO4 became organic upon
> this
> >>> linkage - a PDB chemical conundrum!!).
> >>>
> >>> (3.2) CCDC does not make any attempt to standardise atom
> names nor
> >>> to match same structures to have equal atom names -
> original author
> >>> atom names are kept so that amino acids may have bizarre
> atom names
> >>> and where required symmetry atom names are generated -
> this is rare
> >>> in the PDB but not unknown, and the PDB is poor at
> completing
> >>> atom/ligand names where symmetry is required and in fact
> often is
> >>> not completed in any chemical reasonable sense as this
> would require changes in occupancy.
> >>>
> >>> The simplest case is in racemic PDB entries where the
> symmetry
> >>> generated structure for say L-ALA should be the D-version
> DAL, but
> >>> PDB as is, has not coped with it, as it would require two
> sets of
> >>> coordinates each at say 1/2 occupancy (usually).
> >>>
> >>> One of several examples in the PDB archive is pdb entry
> 3e7r. The
> >>> Xray structure of Racemic Plectasin. The entry consists of
> one
> >>> protein chain, in SPG P-1.
> >>>
> >>> In the manuscript
> >>> http://onlinelibrary.wiley.com/doi/10.1002/pro.127/pdf
> >>>
> >>> Figure 3a, for example shows Crystal packing.
> >>> (a) Centrosymmetric P-1 unit cell. The L-plectasin
> molecule is shown
> >>> in blue and the D-plectasin molecule is in gold.
> >>>
> >>> But if you use the PDB entry, and the symmetry operator of
> P-1 to
> >>> generate the two symmetry related mates in the unit cell
> you will
> >>> get a chain with L- naming residues
> >>> GLY-PHE-GLY-CYS-ASN-GLY-PRO-........ etc representing D-
> amino
> >>> acids.
> >>> (GLY is a special case).
> >>>
> >>> (3.3) There is also the problem in assigning a 3-letter
> code where
> >>> the submission has obviously assigned the wrong chirality.
> One
> >>> example is a where the sugar must be NAG but is assigned
> NGA in a
> >>> glycopeptide where NGA is impossible - the PDB should have
> assigned
> >>> NAG with a CAVEAT that the chirality is incorrect. Note,
> >>> re-refinement by other software will require a
> bond-breakage.
> >>> NGA is used in 90 entries (RCSB counting 21-June-2015)
> >>>
> >>> regards Miri
> >>>
> >>>
> >>>
> >>>
> >>>>> From: Yong Wang <[log in to unmask]>
> >>>>> Reply-to: Yong Wang <[log in to unmask]>
> >>>>> To: [log in to unmask]
> >>>>> Subject: Re: [ccp4bb] FW: New ligand 3-letter code
> (help-7071)
> >>>>> Date: Sat, 20 Jun 2015 18:36:34 +0000
> >>>>>
> >>>>> Sharing a ligand name should only be limited to having
> the same
> >>>>> compound, i.e. same 2D structure or connectivity. Each
> deposition
> >>>>> should have its own 3D coordinates. If a different
> publication
> >>>>> gets your ligand 3D coordinates ("2Y59 actually embodies
> the
> >>>>> atomic coordinates from the 2Y2I"), that looks to me an
> oversight
> >>>>> by PDB. It is hard to believe that PDB intended to use
> the 3D
> >>>>> coordinates from one entry for the other, ligand or not.
> In fact,
> >>>>> the restraints as described by the ligand dictionary
> should also be kept separate as that reflects how the authors
> refine their ligand.
> >>>>>
> >>>>> Yong
> >>>>>
> >>>>> -----Original Message-----
> >>>>> From: CCP4 bulletin board [mailto:[log in to unmask]]
> On Behalf
> >>>>> Of Martyn Symmons
> >>>>> Sent: Friday, June 19, 2015 8:39 PM
> >>>>> To: [log in to unmask]
> >>>>> Subject: Re: [ccp4bb] FW: New ligand 3-letter code
> (help-7071)
> >>>>>
> >>>>> By oversimplifying the situation here the PDB does not
> answer my
> >>>>> related point about competing crystallographers:
> >>>>> My scenario:
> >>>>>
> >>>>> Group A deposits structure with new drug - gets their
> three-letter
> >>>>> code for example ZA3 they then get to check the
> coordinates and
> >>>>> chemical definition of this ligand.
> >>>>>
> >>>>> But suppose a little after that a competing group B
> deposits their
> >>>>> structure with the same drug which they think is novel -
> but no...
> >>>>> they get assigned the now described ZA3 which has been
> checked by
> >>>>> the other group.
> >>>>>
> >>>>> Then it is a race to see who gets to publish and
> release first.
> >>>>> And if it is the second group B who wins then they are
> publishing
> >>>>> the work of their A competitors - who have done the
> depositing and
> >>>>> checking of the ligand description.
> >>>>>
> >>>>> Sounds unlikely? Well, it actually happened in 2011
> for my exact
> >>>>> example ZA3 - present in 2Y2I and in 2Y59 from competing
> groups.
> >>>>>
> >>>>> From the dates in the mmcif it was 2Y2I depositors who
> set up
> >>>>> and had a chance to review the description of ZA3
> ligand. Only to
> >>>>> see it released a week before their crystal structure,
> when their
> >>>>> ZA3 appeared to accompany competing 2Y59! It is amazing
> that the
> >>>>> PDB did not spot this and arrange a suitable workaround.
> >>>>>
> >>>>> Just to check:
> >>>>> mmcif for ZA3 shows it was created for 2Y2I:
> >>>>> ...
> >>>>> _chem_comp.pdbx_model_coordinates_db_code 2Y2I
> >>>>> ...
> >>>>> But it was modified for release:
> >>>>> ...
> >>>>> _chem_comp.pdbx_modified_date
> 2011-07-22
> >>>>> ...
> >>>>> corresponding to the early 2011-07-27 release date of
> the
> >>>>> competing
> >>>>> structure: 2Y59 even though this PDB was _deposited_
> second.
> >>>>>
> >>>>> The ZA3 ligand definition released with 2Y59 actually
> embodies the
> >>>>> atomic coordinates from the 2Y2I structure:
> >>>>>
> >>>>> <mmcif>
> >>>>> ZA3 O6 O6 O 0 1 N N N 8.279 7.165 40.963 0.311
> -1.061 -0.920
> >>>>> O6 ZA3 1
> >>>>> ZA3 C5 C5 C 0 1 N N N 9.132 8.047 40.908 0.147
> -0.205 -0.073
> >>>>> C5 ZA3 2 ...
> >>>>> <PDB 2Y2I>
> >>>>> HETATM 3598 O6 ZA3 A1000 8.279 7.165 40.963
> 1.00 41.25
> >>>>> O
> >>>>> HETATM 3599 C5 ZA3 A1000 9.132 8.047 40.908
> 1.00 63.20
> >>>>> C ...
> >>>>>
> >>>>> Surely a better approach would be to allow both groups a
> chance to
> >>>>> work through and sign off on independent ligand
> descriptions?
> >>>>>
> >>>>> Then whoever releases first would release both a novel
> structure
> >>>>> and the ligand definition _they_ deposited and checked.
> Their
> >>>>> priority can then be asserted and the other group
> contacted to ask
> >>>>> if they agree to accept this definition. This also has
> the
> >>>>> advantage of better confidentiality pre-publication.
> >>>>>
> >>>>> Another problem from any cross-linking of definitions is
> that say
> >>>>> group A are motivated by reviewers' reports to change
> the
> >>>>> definition of ZA3 pre-release. Well now the change
> impinges on the
> >>>>> chemical meaning of other group B's deposited structure.
> For example ZA3 mmcif has a statement:
> >>>>>
> >>>>> ZA3 "Modify aromatic_flag" 2011-06-04 RCSB
> >>>>>
> >>>>> so this change was pre-release - but we cannot be sure
> what
> >>>>> motivated this - whether it was signed off by the 2Y2I
> authors or
> >>>>> the 2Y59 authors (or both?)....
> >>>>>
> >>>>> With the accelerating pace of drug discovery for sure
> this sort of
> >>>>> uncertainty is going to happen again.Unless the PDB have
> changed
> >>>>> their practice for ligand deposition?
> >>>>>
> >>>>> All the best
> >>>>> Martyn
> >>>>>
> >>>>> Cambridge.
> >>>>>
> >>>>> On Fri, Jun 19, 2015 at 1:49 PM, Sheriff, Steven
> >>>>> <[log in to unmask]> wrote:
> >>>>>>
> >>>>>> All:
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> Since the original query was cross-posted on both the
> COOT
> >>>>>> mailing list and the CCP4BB Rachel Green gave me
> permission to
> >>>>>> forward this to both. She provides links about the
> mechanism of
> >>>>>> assignment of 3-letter codes. In the third link below,
> my
> >>>>>> original suggestion to the COOT mailing list that one
> could just
> >>>>>> use UNK is incorrect as that is reserved for unknown
> amino acids.
> >>>>>> According to this document, I should have suggested UNL
> for an
> >>>>>> unknown ligand.
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> Steven
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> From: Rachel Kramer Green
> [mailto:[log in to unmask]]
> >>>>>> Sent: Tuesday, June 16, 2015 10:21 AM
> >>>>>> To: Sheriff, Steven
> >>>>>> Cc: info
> >>>>>> Subject: Re: New ligand 3-letter code (help-7071)
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> Dear Steven,
> >>>>>>
> >>>>>> During annotation of ligands, all chemical components
> present in
> >>>>>> the structure are compared against the definitions in
> the
> >>>>>> Chemical Component Dictionary
> (http://www.wwpdb.org/data/ccd). If
> >>>>>> the ligand is not in the dictionary, a three letter
> code is
> >>>>>> assigned. See
> >>>>>>
> http://www.wwpdb.org/documentation/policy#toc_assignment. In
> the
> >>>>>> future, a group of three-letter codes may be set aside
> to be used during refinement to flag new ligands.
> >>>>>>
> >>>>>> Clarification about the ligand ids assignment and in
> particular
> >>>>>> the usage of UNX/UNL/UNK residues can be found at
> >>>>>> http://www.wwpdb.org/documentation/procedure#toc_2.
> >>>>>>
> >>>>>> Best wishes,
> >>>>>> Rachel
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> ________________________________
> >>>>>>
> >>>>>> Rachel Kramer Green, Ph.D.
> >>>>>>
> >>>>>> RCSB PDB
> >>>>>>
> >>>>>> [log in to unmask]
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> New! Deposit X-ray data with the wwPDB at:
> >>>>>>
> >>>>>> http://deposit.wwpdb.org/deposition (NMR and 3DEM
> coming soon).
> >>>>>>
> >>>>>>
> ___________________________________________________________
> >>>>>>
> >>>>>> Twitter: https://twitter.com/#!/buildmodels
> >>>>>>
> >>>>>> Facebook: http://www.facebook.com/RCSBPDB
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> On 6/5/2015 7:50 AM, Sheriff, Steven wrote:
> >>>>>>
> >>>>>> All:
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> Why the concern for unassigned three-letter codes? The
> wwPDB
> >>>>>> isn’t going to let you assign a three-letter code, it
> will choose
> >>>>>> its own code.
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> At BMS (a pharmaceutical company), we do many hundreds
> of
> >>>>>> structures a year with ligands and we assign the same,
> already
> >>>>>> assigned, three-letter code for all of our ligands
> (unless we
> >>>>>> have two or more different ligands in a single
> structure, in
> >>>>>> which case we use two or more different already
> assigned
> >>>>>> three-letter codes). COOT can mostly handle this.
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> However, I believe that if you want an unassigned code,
> the wwPDB
> >>>>>> has set aside UNK[nown] for this purpose.
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> Steven
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> From: Mailing list for users of COOT Crystallographic
> Software
> >>>>>> [mailto:[log in to unmask]] On Behalf Of Eleanor
> Dodson
> >>>>>> Sent: Friday, June 05, 2015 6:28 AM
> >>>>>> To: [log in to unmask]
> >>>>>> Subject: Re: New ligand 3-letter code
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> I use your method - trial & error..
> >>>>>>
> >>>>>> It would be nice if at least there was a list somewhere
> of
> >>>>>> unassigned codes!
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> On 5 June 2015 at 09:16, Lau Sze Yi (SIgN)
> >>>>>> <[log in to unmask]> wrote:
> >>>>>>
> >>>>>> Hi,
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> What is the proper way of generating 3-letter code for
> a new ligand?
> >>>>>> As of now, I insert my ligand in Coot using smiles
> string and for
> >>>>>> the 3-letter code I picked a non-existent code by trial
> and error
> >>>>>> (not very efficient). A cif file with corresponding
> name which I
> >>>>>> generated using Phenix was imported into Coot.
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> I am sure there is a proper way of doing this.
> Appreciate your
> >>>>>> feedback.
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> Regards,
> >>>>>>
> >>>>>> Sze Yi
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> ________________________________
> >>>>>>
> >>>>>> This message (including any attachments) may contain
> >>>>>> confidential, proprietary, privileged and/or private
> information.
> >>>>>> The information is intended to be for the use of the
> individual
> >>>>>> or entity designated above. If you are not the intended
> recipient
> >>>>>> of this message, please notify the sender immediately,
> and delete
> >>>>>> the message and any attachments. Any disclosure,
> reproduction,
> >>>>>> distribution or other use of this message or any
> attachments by
> >>>>>> an individual or entity other than the intended
> recipient is prohibited.
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> ________________________________
> >>>>>> This message (including any attachments) may contain
> >>>>>> confidential, proprietary, privileged and/or private
> information.
> >>>>>> The information is intended to be for the use of the
> individual
> >>>>>> or entity designated above. If you are not the intended
> recipient
> >>>>>> of this message, please notify the sender immediately,
> and delete
> >>>>>> the message and any attachments. Any disclosure,
> reproduction,
> >>>>>> distribution or other use of this message or any
> attachments by
> >>>>>> an individual or entity other than the intended
> recipient is prohibited.
> >>
> >>
> >
>
>
>
> ________________________________
>
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