[gmx-users] mdsimulation of drug enzyme complex

[Justin A. Lemkul]

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
> 
>     ========================================
>     -- 
>     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

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