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
________________________________
From: CCP4 bulletin board [mailto:[email protected]] On
Behalf Of Joel Tyndall
Sent: Wednesday, February 08, 2012 10:00 PM
To: [email protected]
Subject: Re: [ccp4bb] Generating parameters/cif files for
macrocyclic ligands
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:[email protected]] On
Behalf Of Garib N Murshudov
Sent: Wednesday, 8 February 2012 11:56 p.m.
To: [email protected]
Subject: Re: [ccp4bb] Generating parameters/cif files for
macrocyclic ligands
Hi Joel
Herman is right:
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
libcheck
file_mol <mol_file_name>
nodist y
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.
regards
Garib
On 8 Feb 2012, at 10:33, [email protected] wrote:
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:[email protected]]
On Behalf Of Joel Tyndall
Sent: Tuesday, February 07, 2012 10:44 PM
To: [email protected]
Subject: [ccp4bb] Generating parameters/cif files for
macrocyclic ligands
Hi folks,
I have an intriguing problem. I'm trying to generate a
cif file for a macrocyclic peptide (of the likes in pdb1d4k
<http://www.rcsb.org/pdb/explore/explore.do?structureId=1d4k> ). 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)
Regards
Joel
_________________________________
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
Garib N Murshudov
Structural Studies Division
MRC Laboratory of Molecular Biology
Hills Road
Cambridge
CB2 0QH UK
Email: [email protected] <mailto:[email protected]>
Web http://www.mrc-lmb.cam.ac.uk <http://www.mrc-lmb.cam.ac.uk/>
