Hi Joe,
Non-natural amino acids and links etc. remain a moving target.
Almost every year, refinement programs change the way these things are
specified. Here is how I would do it:
1) search the protein data bank to see if your
non-natural amino acid is already present somewhere.
If yes, use the same residue name and atom names. As it stands
now, the residue is most likely already defined in the libraries that
come with the programs.
2) If not, I would define the monomer as a peptide under
_chem_comp_desc_level. See e.g. $CLIB/data/monomers/c/CGU.cif. This should work.
The cif file itself can be generated with Grade, libchk or
Prodrg.
3) If this
does not work, one can always add more LINK records to make the
connections.
My two cents,
Herman
Hi Garib,
Thanks for that (and thanks
Herman). How do I declare a non-natural amino acid a peptide? My ligand
contains two peptidic cycles (non-N to C) where the side chains are cyclised.
I think I’ll be able to use several linbk records for the connections but the
non-natural amino acid are complicating the issue
_________________________________
Joel
Tyndall, PhD
Senior Lecturer in Medicinal Chemistry
National School
of Pharmacy
University of Otago
PO Box 56 Dunedin 9054
New
Zealand
Skype: jtyndall
http://www.researcherid.com/rid/C-2803-2008
Pukeka
Matua
Te Kura Taiwhanga Putaiao
Te Whare Wananga o Otago
Pouaka
Poutapeta 56 Otepoti 9054
Aotearoa
Ph /
Waea
+64 3 4797293
Fax / Waeawhakaahua +64 3
4797034
From: CCP4
bulletin board [mailto:[log in to unmask]] On Behalf Of Garib N
Murshudov
Sent: Wednesday, 8 February 2012 11:56 p.m.
To:
[log in to unmask]
Subject: Re: [ccp4bb] Generating
parameters/cif files for macrocyclic ligands
If you are refining cyclic peptides then the easiest way is
to use link record linking C-terminus with N terminus. the name of the link
should be TRANS. Here is an example:
LINK ALA S
21
ASN S 1
TRANS
It will force ALA 21 to be linked (with torsion, angles,
planes, bonds etc) to ASN 1 of chain S.
This way you do not have to create description for large
molecule. If you still want to create one molecule and you have mol2 file with
coordinates then you can use libcheck to generate full dictionary using
following commands
It should generate fdescription. However I would prefer
using link record. this way you keep amino acid names etc intact. If you amino
acids are not among existing then you will need to create their description
first and declare them peptide.
Hi
Joel,
The
way I solved this problem was by generating a linear peptide and then
connecting the ends using a LINK card in the header of the
pdb.
Good
luck!
Herman
From: CCP4
bulletin board [mailto:[log in to unmask]] On Behalf Of Joel
Tyndall
Sent: Tuesday, February 07, 2012 10:44
PM
To: [log in to unmask]
Subject: [ccp4bb] Generating parameters/cif
files for macrocyclic ligands
I have an intriguing problem. I’m trying to generate a
cif file for a macrocyclic peptide (of the likes in pdb1d4k).
They are cyclic tripeptides units. I can generate a pdb or mol2 file easily.
I have used PRODRG to generate a .cif file and Coot read thjis in nicely.
However, as it is cyclic one cannot adjust the dihedral angles. I have
previously done this using CNS where you can break the tricyclic peptide
into residues and generate parameters to specify bonds/links between the
residues (which allows this kind of movement). I can’t come up with a way to
do this without using CNS. I have looked ta J-ligand which allows for
one link “between” two separate residues which precludes a macrocycle. I
have looked at sketcher within CCP4 which reads the pdb files but I don’t
believe this can be done here. Within Coot I can refine the whole ligand but
not certain components.
Any suggestions greatly appreciated . ( I may stick to
coot refinement with fixed atoms at this stage)
_________________________________
Joel Tyndall,
PhD
Senior Lecturer in Medicinal Chemistry
National School of
Pharmacy
University of Otago
PO Box 56 Dunedin 9054
New
Zealand
Pukeka
Matua
Te Kura Taiwhanga Putaiao
Te Whare Wananga o Otago
Pouaka
Poutapeta 56 Otepoti 9054
Aotearoa
Ph /
Waea
+64 3 4797293
Fax / Waeawhakaahua +64 3
4797034
Garib
N Murshudov
Structural Studies Division
MRC
Laboratory of Molecular Biology
