On 25/08/2011 3:10 AM, Pablo Englebienne wrote:
Hi all,
I am trying to build a topology for a synthetic molecule that consists
of peptides connected by oligoethyleneglycol (I'll call it PEG)
linkers terminated with an amine and a carboxylic acid:
-NH2-CH2-[CH2-O-CH2]n-CH2-C(=O)-
The system looks like this:
N-(PEG)-C-N-(peptide2)-Lys(C-ter)-NZ-C-(PEG)-N
So:
* the C-terminus of a PEG linker is attached to the N terminus of the
peptide
* the terminal Lys on the peptide is attached to the C-terminus of a
PEG linker
I was able to successfully build a topology for this molecule by:
* defining appropriate residues (for the PEG chains and the Lys with a
PEG attached on the NZ) in a local copy of the forcefield file, adding
the residues' topologies to aminoacids.rtp
* using the specbond.dat file to define the bond between the NZ in the
Lys and the PEG linker
* adding the residues to residuetypes.dat with a "Protein" type
* calling pdb2gmx with the -ter option to assign the protonation states
Now, I need to extend the topology to a molecule like this one:
N-(peptide1)-C-N-(PEG)-C-N-(peptide2)-Lys(C-ter)-NZ-C-(PEG)-N-C-(peptide3)-N
The difficulty with this molecule is that it has 2 N-termini and a
single C-terminus (in the Lys with the PEG attached to the NZ
sidechain). pdb2gmx recognizes the whole molecule as a peptide, but
treats the last residue as a C-terminus, when it actually is an
N-terminus.
I found in the description for specbond.dat
(http://www.gromacs.org/Documentation/File_Formats/specbond.dat) that
for a branched peptide the "-chainsep" option of pdb2gmx can be used,
so I started to work on that. I split the molecules in 2 chains like
this:
N-(peptide1)-C-N-(PEG)-C-N-(peptide2)-Lys(C-ter)-NZ- ||
-C-(PEG)-N-C-(peptide3)-N
I reversed the order of the residues in the second chain, so that the
residues are in N-to-C order. With this, pdb2gmx recognizes the proper
termini when called as:
$ pdb2gmx -f substrate_edited-reversed.pdb -ter -chainsep interactive
I tried setting the protonation of the termini as charged for the
"real" termini and None for the artificial one (the one that should be
handled by specbond.dat), but I get an error message:
---[pdb2gmx output]---
[...]
Splitting PDB chains based on TER records or changing chain id.
Merge chain ending with residue LYSS27 (chain id ' ', atom 71 NZ) with
chain starting with residue GLU28 (chain id 'p', atom 308 OE2)? [n/y]
n
Merged 1 chains into one molecule definition
There are 2 chains and 0 blocks of water and 47 residues with 303 atoms
chain #res #atoms
1 ' ' 27 198
2 'p' 17 105
[...]
Identified residue ARG1 as a starting terminus.
Identified residue LYSS27 as a ending terminus.
9 out of 9 lines of specbond.dat converted successfully
Special Atom Distance matrix:
PEA118
CG1125
LYSS27 NZ198 2.762
That's a long bond. Does your reference length in specbond.dat suit it?
IIRC there should be some evidence in the output of the special bond
being formed if it actually is. If not, your symptoms are probably related.
Oh, and well done for constructing a good question. You would likely not
have gotten anywhere giving less detail :)
Mark
Select start terminus type for ARG-1
0: NH3+
1: NH2
2: None
0
Start terminus ARG-1: NH3+
Select end terminus type for LYSS-27
0: COO-
1: COOH
2: None
0
End terminus LYSS-27: COO-
[...]
Identified residue GLU28 as a starting terminus.
Identified residue PEA47 as a ending terminus.
9 out of 9 lines of specbond.dat converted successfully
Select start terminus type for GLU-28
0: NH3+
1: NH2
2: None
0
Start terminus GLU-28: NH3+
Select end terminus type for PEA-47
0: COO-
1: COOH
2: None
2
End terminus PEA-47: None
[...]
-------------------------------------------------------
Program pdb2gmx, VERSION 4.5.4
Source code file: pdb2top.c, line: 1035
Fatal error:
There is a dangling bond at at least one of the terminal ends. Select
a proper terminal entry.
For more information and tips for troubleshooting, please check the
GROMACS
website at http://www.gromacs.org/Documentation/Errors
-------------------------------------------------------
---[pdb2gmx output]---
I think that the problem might stem from the fact that the C-terminus
in the second chain is not a real peptide; I changed residuetypes.dat
to have the PEG residues as "Other", which causes pdb2gmx to recognize
the last aminoacid as a C-terminus, but treating it as "None" yields
the same error. Unfortunately, there is nothing about this error in
http://www.gromacs.org/Documentation/Errors .
Any suggestions on how to make this work will be greatly appreciated!
--
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