[gmx-users] mdsimulation of drug enzyme complex

Justin A. Lemkul jalemkul at vt.edu
Fri Apr 9 15:54:55 CEST 2010



abhijit kayal wrote:
> 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 

Since you have two different ligands, you will inherently have two 
[moleculetype] definitions, between which no bonded interactions can be 
specified.  You should take another look at the atoms mdrun is complaining 
about; I see no possible way that they can belong to atoms of different molecules.

To ultimately solve the problem, refer to the "blowing up" link I provided 
before.  Something about your model physics (parameters, .mdp settings, etc) is 
unrealistic.

-Justin

>                                                                          
>                                                    Abhijit
>                                                                          
>  
> 
> On Fri, Apr 9, 2010 at 6:33 PM, Justin A. Lemkul <jalemkul at vt.edu 
> <mailto: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>
>         <mailto: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> <http://vt.edu> | (540)
>         231-9080
> 
>            http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
>            ========================================
>            --     gmx-users mailing list    gmx-users at gromacs.org
>         <mailto:gmx-users at gromacs.org>
>            <mailto:gmx-users at gromacs.org <mailto:gmx-users at gromacs.org>>
> 
>            http://lists.gromacs.org/mailman/listinfo/gmx-users
>            Please search the archive at http://www.gromacs.org/search before
>            posting!
>            Please don't post (un)subscribe requests to the list. Use the www
>            interface or send it to gmx-users-request at gromacs.org
>         <mailto:gmx-users-request at gromacs.org>
>            <mailto:gmx-users-request at gromacs.org
>         <mailto:gmx-users-request at gromacs.org>>.
> 
>            Can't post? Read http://www.gromacs.org/mailing_lists/users.php
> 
> 
> 
>     -- 
>     ========================================
> 
>     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
> 
>     ========================================
>     -- 
>     gmx-users mailing list    gmx-users at gromacs.org
>     <mailto:gmx-users at gromacs.org>
>     http://lists.gromacs.org/mailman/listinfo/gmx-users
>     Please search the archive at http://www.gromacs.org/search before
>     posting!
>     Please don't post (un)subscribe requests to the list. Use the www
>     interface or send it to gmx-users-request at gromacs.org
>     <mailto:gmx-users-request at gromacs.org>.
>     Can't post? Read http://www.gromacs.org/mailing_lists/users.php
> 
> 

-- 
========================================

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

========================================



More information about the gromacs.org_gmx-users mailing list