[gmx-users] Disulphide bonded cyclic peptides

[Sahil Lall]

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.

> 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? 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?

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
>> --