[gmx-users] Re: disulfide bridge broken during EM

Justin A. Lemkul jalemkul at vt.edu
Thu Mar 10 14:39:22 CET 2011

Anna Marabotti wrote:
>  Dear Justin,
> thank you very much. Yes for sure bonds do not "break" during EM (I should
> have better said "disappear"), that's why it looked strange to me. In any
> case, I will do the check: if this bond will fall outside specifications in
> specbond.dat I will conclude that it is only a crystallographic artefact
> (and I will be very happy because in that way I can use only the monomer of
> the protein to do simulations...)

I would not consider the parameters in specbond.dat to be definitive proof of a 
non-existent disulfide.  If the distance between the S atoms is considerably 
more than 0.2 nm (with 0.205 nm being "average" for a disulfide), then you may 
have some justification.  But if the rationale is "Gromacs didn't think there 
should be a disulfide, so that's reality," I'd imagine most reviewers would be 
extremely skeptical.


> Anna
> -----Messaggio originale-----
> Da: gmx-users-bounces at gromacs.org [mailto:gmx-users-bounces at gromacs.org] Per
> conto di gmx-users-request at gromacs.org
> Inviato: giovedì 10 marzo 2011 14.15
> A: gmx-users at gromacs.org
> Oggetto: gmx-users Digest, Vol 83, Issue 66
> Message: 3
> Date: Thu, 10 Mar 2011 08:13:06 -0500
> From: "Justin A. Lemkul" <jalemkul at vt.edu>
> Subject: Re: [gmx-users] disulfide bridge broken during EM
> To: Discussion list for GROMACS users <gmx-users at gromacs.org>
> Message-ID: <4D78CE62.2010601 at vt.edu>
> Content-Type: text/plain; charset=ISO-8859-1; format=flowed
> Anna Marabotti wrote:
>> Dear all,
>> I have a PDB file of a protein that is in dimeric form, with an 
>> INTERchain disulphide bridge. However, in their paper the 
>> crystallographers are not sure if this is a true dimeric form or a 
>> cyrstallographic artefact (PQS server suggests it is a true dimeric 
>> form, but with low confidence). I'm preparing this protein to do MD 
>> simulations in water, so I used pdb2gmx, editconf, genbox, genion..and 
>> all worked properly (no error messages). Then I launched grompp+mdrun to 
>> do a mild minimization before MD: all worked properly with no error 
>> messages, but when I had a look at the final .gro file, I saw that the 
>> disulphide bridge was broken (before this step, it was present). Looking 
>> at the trajectory, I found that the bridge broke at the first step of 
>> the minimization. However, I did not have any error message, the 
>> minimization worked regularly.
>> I would like to know if my starting structure is a real dimeric 
>> structure, or not, therefore I would like to know if the disulphide 
>> bridge broke because it is only an artefact, or not. Do I have to add 
>> some special constraints to the topology and/or .mdp file in order to 
>> preserve the disulphide bridge in "normal" simulations, or not? I had a 
>> look in the gmx-users list, but I only see suggestions to introduce a 
>> new disulphide bridge (and the messages seem quite old, probably 
>> referred to the Gromacs 3 version, whereas I'm currently using version 
>> 4.0.3). In a very old message (2001) there is the statement "pdb2gmx can 
>> *not* make inter-molecular bonds" however, in this case, the bond is 
>> already present in the crystal and is kept in all phases until the 
>> minimization. I tried to use pdb2gmx -ss in order to set interactively 
>> the SS bridge selection, but nothing happened: the program does not ask 
>> me any prompt. Any suggestions?
> Bonds do not break and form during EM or MD, which must obey classical 
> mechanics.  If you saw a "bond" there, it was just an effect of the 
> visualization software.  The true answer is if there is a bond written in
> the 
> [bonds] section of your topology.  While true that Gromacs cannot make bonds
> between molecules, you can use pdb2gmx -merge (-chainsep in version 4.5 and
> up) 
> to make multiple molecules part of the same [moleculetype].  If you have 
> individual chain topologies from pdb2gmx, then there was never a bond there.
> If 
> the two atoms fall outside the tolerance range specified in specbond.dat, no
> bond will have been created.
>> Many thanks and best regards
>> Anna Marabotti
>> PS BTW: often when I'm searching in the gmx-users list I see the 
>> suggestions to some links (for example in the message in 
>> http://lists.gromacs.org/pipermail/gmx-users/2008-March/032662.html Mark 
>> Abraham suggests to explore 
>> http://wiki.gromacs.org/index.php/specbond.dat but when I click on the 
>> link, I am redirected to the www.gromacs.org <http://www.gromacs.org> 
>> website. Even if I copy the link directly in a new browser window, I 
>> cannot see the original link. Why?
> The website has undergone several major overhauls since 2008.  You can
> search 
> the current Gromacs website for specbond.dat and retrieve:
> http://www.gromacs.org/Documentation/File_Formats/specbond.dat
> -Justin
>> __________________________________________________________________
>> Anna Marabotti, Ph.D.
>> Laboratory of Bioinformatics and Computational Biology
>> Institute of Food Science - CNR
>> Via Roma, 64
>> 83100 Avellino
>> Phone: +39 0825 299651
>> Fax: +39 0825 781585
>> E-mail: amarabotti at isa.cnr.it <mailto:amarabotti at isa.cnr.it>
>> Skype account: annam1972
>> Web site: http://bioinformatica.isa.cnr.it/anna/anna.htm
>> "When a man with a gun meets a man with a pen, the man with the gun is a 
>> dead man"


Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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