[gmx-users] Disulphide bonded cyclic peptides
Alessandra Villa
alessandra.villa.biosim at gmail.com
Fri Nov 29 11:16:48 CET 2019
Hi,
On Fri, Nov 29, 2019 at 8:30 AM Sahil Lall <slall at ncbs.res.in> wrote:
> Hello,
>
> Thank you for your suggestions, gave me some insight into my own work.
> However, the problem still persists.
>
> > 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?
>
> Removing the -ter option does not work in any combination. It always
> overrides everything else and breaks the cyclising peptide bond into
> NH3+ and COO-.
>
> .
>
> > 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)
>
> So this also does not work. pdb2gmx breaks the peptide bond without the
> -ter option.
>
> I tried putting a new entry in the OPLS aminoacids.n.tdb file as you
> suggested. I used the opls_910 planar hydrogen for secondary amines as
> shown below
>
> [ CYS2-NH ]
> [ replace ]
> N opls_900 14.0027 -0.9
> CA opls_912B 12.011 0.12
> [ add ]
> 1 1 H N CA C
> opls_910 1.008 0.36
> [ delete ]
> H
>
>
You got a charged system, probably because you have generated a new entry
without accounting for the partial charge.
As atomic charge and atom types I suggest to use the one of the backbone
for your new entry (since you do not have a real termini) for CYS-1
N opls_238 -0.500 0
H opls_241 0.300 0
CA opls_224B 0.140 1
You could also directly change the charges in the top file.
I hope this solve the problem
Best regards
Alessandra
Now I can get the peptide bond correctly but the system is charged.
> Output below:
>
> Identified residue CYS1 as a starting terminus.
> Identified residue CYS6 as a ending terminus.
> 2 out of 2 lines of specbond.dat converted successfully
> Special Atom Distance matrix:
> CYS1 CYS1 CYS1 CYS6 CYS6
> N1 C3 SG6 N87 C89
> CYS1 C3 0.244
> CYS1 SG6 0.312 0.419
> CYS6 N87 0.335 0.510 0.486
> CYS6 C89 0.136 0.373 0.322 0.239
> CYS6 SG92 0.387 0.482 0.205 0.420 0.365
> Linking CYS-1 N-1 and CYS-6 C-89...
> Linking CYS-1 SG-6 and CYS-6 SG-92...
> Select start terminus type for CYS-1
> 0: CYS2-NH
> 1: NH3+
> 2: ZWITTERION_NH3+ (only use with zwitterions containing exactly one
> residue)
> 3: NH2
> 4: None
> 0
> Start terminus CYS-1: CYS2-NH
> Select end terminus type for CYS-6
> 0: COO-
> 1: ZWITTERION_COO- (only use with zwitterions containing exactly one
> residue)
> 2: COOH
> 3: None
> 3
> End terminus CYS-6: None
> Checking for duplicate atoms....
> Generating any missing hydrogen atoms and/or adding termini.
> Now there are 6 residues with 96 atoms
> Making bonds...
> Number of bonds was 99, now 98
> Generating angles, dihedrals and pairs...
> Before cleaning: 258 pairs
> Before cleaning: 258 dihedrals
> Keeping all generated dihedrals
> Making cmap torsions...There are 258 dihedrals, 21 impropers, 174 angles
> 255 pairs, 98 bonds and 0 virtual sites
> Total mass 734.892 a.m.u.
> Total charge -0.420 e
> Writing topology
>
> Any ideas?
>
> Extremely thankful
>
> Sahil
>
> On 2019-11-28 20:15, Alessandra Villa wrote:
>
> > 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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