[gmx-users] Disulphide bonded cyclic peptides

[Alessandra Villa]

Hi again,

On Thu, Nov 28, 2019 at 11:06 AM Sahil Lall <slall at ncbs.res.in> wrote:

> Hello,
>
> I am extremely thankful for your suggestions, but I have a few concerns
> with your advice as stated below.
>
> > Hi,
> > Below some suggestion that may help you.
> >
> > On Wed, Nov 27, 2019 at 7:44 AM Sahil Lall <slall at ncbs.res.in> wrote:
> >
> >> Dear community,
> >>
> >> I want to use the OPLS-AA ff to understand the dynamics of a cyclic
> >> peptide with terminal Cystines that are disulphide linked. To cyclise
> >> the N- and C- termini, I used a special bond in a specbond.dat file
> >> placed in my working directory.
> >>
> >> 2
> >> CYS N 1 CYS C 1 0.14 CYS CYS
> >> CYS SG 1 CYS SG 1 0.2 CYS2 CYS2
> >>
> >> and after the pdb2gmx command I get the following response
> >>
> >> Identified residue CYS2 as a starting terminus.
> >> Identified residue CYS7 as a ending terminus.
> >> 2 out of 2 lines of specbond.dat converted successfully
> >> Special Atom Distance matrix:
> >> CYS2    CYS2    CYS2    CYS7    CYS7
> >> N1      C3     SG6     N45     C47
> >> CYS2      C3   0.244
> >> CYS2     SG6   0.312   0.419
> >> CYS7     N45   0.335   0.510   0.486
> >> CYS7     C47   0.136   0.373   0.322   0.239
> >> CYS7    SG50   0.387   0.482   0.205   0.420   0.365
> >> Linking CYS-2 N-1 and CYS-7 C-47...
> >> Linking CYS-2 SG-6 and CYS-7 SG-50...
> >>
> >> However, the problem arises with the -ter flag in the pdb2gmx command
> >>
> >> pdb2gmx -f in.pdb -o out.gro -ter -ignh
> >>
> >> With the option -ignh, you request pdb2gmx to add H atom. Thus, if you
> > have  already H atoms in the pdb I suggest to remove the option -ignh.
>
> I had already tried removing the -ignh option before posting this here
> but did not find success.
>
> Did you try also without -ter?


> > In alternative,  you could try add a new entry in the file opls force
> field
> > file aminoacids.n.tdb for your CYS termini (e.i in place of NH2 put NH).
> In
> > alternative you can use the file that you got using NH2 as N-terminus,
> and
> > manually remove the extra H you  have connected to N (both from top and
> gro
> > file). This operation requires to be very careful since you have to
> remove
> > the correct H.
>
> If I remove the extra hydrogen after getting the pdb2gmx output, will I
> not have to edit the topology file also?


Yes you should fix also the top file, including  removing all the
interactions that involve the removed H

Another option could be to remove the extra H from gro/pdb file you got
from pdb2gmx, remove H, (if you want, fix the atom number using editconf),
then try to use the so obtained pdb/gro file as input to pdb2gmx (without
-ter -ignh)



> And will changing the CYS
> termini in the force field .tdb file not mess with anything else as far
> as the force field parameters are concerned?
>
>
If properly done, no

Best regards
Alessandra

> Thankful,
>
> Sahil
>
> > Best regards
> > Alessandra
> >
> >> The output is fine and links the terminal Cystines and putting a
> disulphide bond between them as shown above. But doesn't seem to be
> >> happy with the -ter command.
> >>
> >> Select start terminus type for CYS-2
> >> 0: NH3+
> >> 1: ZWITTERION_NH3+ (only use with zwitterions containing exactly one
> >> residue)
> >> 2: NH2
> >> 3: None
> >> 3
> >> Start terminus CYS-2: None
> >> Select end terminus type for CYS-7
> >> 0: COO-
> >> 1: ZWITTERION_COO- (only use with zwitterions containing exactly one
> >> residue)
> >> 2: COOH
> >> 3: None
> >> 3
> >> End terminus CYS-7: None
> >>
> >> -------------------------------------------------------
> >> Program pdb2gmx, VERSION 4.6.7
> >> Source code file:
> >> /home/ncbs/Downloads/gromacs-4.6.7/src/kernel/pdb2top.c, line: 1109
> >>
> >> Fatal error:
> >> There is a dangling bond at at least one of the terminal ends. Fix your
> >> coordinate file, add a new terminal database entry (.tdb), or select the
> >> proper existing terminal entry.
> >> For more information and tips for troubleshooting, please check the
> >> GROMACS
> >> website at http://www.gromacs.org/Documentation/Errors
> >> -------------------------------------------------------
> >>
> >> I cannot understand what is going wrong. The command only works if I
> >> choose NH2 as my N-terminus, however that in principle violates the
> >> neutrality of the system.
> >
> >> Thanks,
> >>
> >> Sahil
> >> --
> --
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