[gmx-users] mdsimulation of drug enzyme complex

abhijit kayal kayalabhijitiitd at gmail.com
Fri Apr 9 15:41:39 CEST 2010


Hi Justin,
            No my ligand is different. And my topolgy  look like this
                             #include "ffG43a1.itp"
                             #include "rrg.itp"
                             #include "drg.itp"
                         and at the end it is like this

                                        Protein             1
                                        RRG                 1
                                        DRG                 1
                                        SOL             17662
           But I cannot understand where my topology is wrong.
             What I  did is that I docked a ligand at active site then
another ligand at the active site. Then I separate the ligands coordinate
and generate .gro,.itp file using PRODRG server.
                                 Please reply

                                               Abhijit



On Fri, Apr 9, 2010 at 6:33 PM, Justin A. Lemkul <jalemkul at vt.edu> wrote:

>
>
> abhijit kayal wrote:
>
>> Hi
>>      Thank you for your quick reply. As you mentioned I went through the
>> mailing list search. And I am thinking my error occured at the system
>> preparation with taking the two ligands. Earlier I ran md simulation  taking
>> the ligand individually and it was showing no error. So the topolgy I got
>> from the PRODRG server is fine. So input file may
>>
>
> Be prepared to justify that the topology is "fine" to a reviewer.  Every
> time I have generated a PRODRG topology, some aspect of its atom types,
> charges, or charge groups has been wrong.  You always need to prove your
> parameters are valid (hence the link I posted) or else you are wasting a lot
> of time doing meaningless MD with a flawed physical model.
>
>
>  be error because GROMACS took both drug as a single one. So please help me
>> how to take the input pdb file that it does not take a single ligand.
>>
>>
> I have no idea.  Are your ligands different?  The same?  If they're the
> same, then there is absolutely no reason why you can't simply:
>
> #include "ligand.itp"
>
> [ molecules ]
> LIG     2
>
> Without seeing your topology or getting a better sense of what it is you
> did, there's not much more to offer.  GROMACS isn't magically converting one
> molecule into two; somehow the instructions you're providing grompp and/or
> mdrun are causing the problem.
>
> -Justin
>
>  On Fri, Apr 9, 2010 at 5:46 PM, Justin A. Lemkul <jalemkul at vt.edu<mailto:
>> jalemkul at vt.edu>> wrote:
>>
>>
>>
>>    abhijit kayal wrote:
>>
>>        Hello everybody,
>>                                I am going to simulate an enzyme complex
>>        taking a ligand at active site and another ligand at allosteric
>>        site. When I ran md simulation taking ligand at active site only
>>        then it was ok. But when I am running the simulation taking both
>>        the ligand it is showing error "1-4 interaction between 3481 and
>>        3485 at distance 4.979 which is larger than the 1-4 table size
>>        2.000 nmThese are ignored for the rest of the simulation.This
>>        usually means your system is exploding,if not, you should
>>        increase table-extension in your mdp file or with user tables
>>        increase the table size". When I look the particular atoms they
>>        corrospond to the last atom of the ligand at the active site
>>        and the fourth atom the ligand at the allosteric site. So I can
>>        not understand why GROMACS takes into account bcause they are
>>        far apart or is there any wrong to my pdb file. I am genereting
>>        the coordinate and topology using PRODRG server. I am also
>>        attached my input pdb file.
>>
>>             Please help me to find out the problem.
>>
>>
>>
>>    Have you looked into the list archive?  This "blowing up" error has
>>    been reported, diagnosed, and solved hundreds (if not thousands) of
>>    times, and there are only a few reasons why it's happening.  Also:
>>
>>    http://www.gromacs.org/Documentation/Terminology/Blowing_Up
>>
>>     >From your description, it sounds as if the topology is constructed
>>    incorrectly, since your two separate ligands are being considered
>>    one molecule and thus experiencing intramolecular 1-4 interactions.
>>     Also note (as I've said dozens of times), face-value PRODRG
>>    topologies are often unsatisfactory (and thus unreliable) without
>>    modification of charges and charge groups.  See here:
>>
>>    http://www.gromacs.org/Documentation/How-tos/Parameterization
>>
>>    -Justin
>>
>>
>>
>>                 Abhijit
>>
>>
>>    --     ========================================
>>
>>    Justin A. Lemkul
>>    Ph.D. Candidate
>>    ICTAS Doctoral Scholar
>>    MILES-IGERT Trainee
>>    Department of Biochemistry
>>    Virginia Tech
>>    Blacksburg, VA
>>    jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080
>>
>>    http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>>
>>    ========================================
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>>
>>
> --
> ========================================
>
> Justin A. Lemkul
> Ph.D. Candidate
> ICTAS Doctoral Scholar
> MILES-IGERT Trainee
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>
> ========================================
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