[gmx-users] md with multiple ligands

[Justin Lemkul]

On 2/14/13 1:20 AM, Ansuman Biswas wrote:
> ---------------------------- Original Message ----------------------------
> Subject: Re: gmx-users Digest, Vol 106, Issue 68
> From:    ansuman at localhost
> Date:    Thu, February 14, 2013 10:16 am
> To:      gmx-users at gromacs.org
> --------------------------------------------------------------------------
>
>
>>
>> Message: 8
>> Date: Wed, 13 Feb 2013 08:28:00 -0500
>> From: Justin Lemkul <jalemkul at vt.edu>
>> Subject: Re: [gmx-users] md with multiple ligands
>> To: Discussion list for GROMACS users <gmx-users at gromacs.org>
>> Message-ID: <511B94E0.4040800 at vt.edu>
>> Content-Type: text/plain; charset=ISO-8859-1; format=flowed
>>
>>
>>
>> On 2/13/13 5:24 AM, Ansuman Biswas wrote:
>>>
>>> Dear gromacs users,
>>>
>>> I wish to run a protein ligand md in Gromacs 4.5.3 with charmm force
>>> field. Its a dimeric protein with a MG ion and 2 ligands bound to two
>>> active sites. I wish to run the dimer and there would be 4 ligands. I
>>> generated the topology files (.itp) of ligands using SWISSPARAM. Before
>>> running the energy minimization I changed the topol.top file accordingly
>>> as mentioned in the SWISSPARAM website. I added all the itp files
>>> together.But while running GROMPP I got an error message like,
>>>
>>>
>>> WARNING 1 [file ADP.itp, line 24]:
>>>     Overriding atomtype NPYL
>>>
>>>
>>> WARNING 2 [file ADP.itp, line 25]:
>>>     Overriding atomtype C5A
>>>
>>>
>>> WARNING 3 [file ADP.itp, line 26]:
>>>     Overriding atomtype N5B
>>>
>>>
>>> WARNING 4 [file ADP.itp, line 27]:
>>>     Overriding atomtype C5B
>>>
>>>
>>> WARNING 5 [file ADP.itp, line 28]:
>>>     Overriding atomtype CB
>>>
>>>
>>> WARNING 6 [file ADP.itp, line 29]:
>>>     Overriding atomtype NPYD
>>>
>>>
>>> WARNING 7 [file ADP.itp, line 30]:
>>>     Overriding atomtype PO4
>>>
>>>
>>> WARNING 8 [file ADP.itp, line 31]:
>>>     Overriding atomtype O2CM
>>>
>>>
>>> WARNING 9 [file ADP.itp, line 32]:
>>>     Overriding atomtype OR
>>>
>>>
>>> WARNING 10 [file ADP.itp, line 33]:
>>>     Overriding atomtype CR
>>>
>>>
>>> WARNING 11 [file ADP.itp, line 34]:
>>>     Overriding atomtype NC=C
>>>
>>>
>>> WARNING 12 [file ADP.itp, line 35]:
>>>     Overriding atomtype HCMM
>>>
>>>
>>> WARNING 13 [file ADP.itp, line 36]:
>>>     Overriding atomtype HNCO
>>>
>>>
>>> WARNING 14 [file ADP.itp, line 37]:
>>>     Overriding atomtype HOCO
>>>
>>>
>>> WARNING 15 [file ADP.itp, line 38]:
>>>     Overriding atomtype HOR
>>>
>>>
>>> WARNING 16 [file ADP.itp, line 43]:
>>>     Overriding atomtype PO4
>>>
>>>
>>> WARNING 17 [file ADP.itp, line 44]:
>>>     Overriding atomtype O2CM
>>>
>>>
>>> WARNING 18 [file ADP.itp, line 45]:
>>>     Overriding atomtype OR
>>>
>>>
>>> WARNING 19 [file ADP.itp, line 46]:
>>>     Overriding atomtype CR
>>>
>>>
>>> WARNING 20 [file ADP.itp, line 48]:
>>>     Overriding atomtype HCMM
>>>
>>>
>>> WARNING 21 [file ADP.itp, line 49]:
>>>     Overriding atomtype HOR
>>>
>>>
>>> WARNING 22 [file ADP.itp, line 50]:
>>>     Overriding atomtype HOCO
>>>
>>>
>>> WARNING 23 [file ADP.itp, line 52]:
>>>     Overriding atomtype NC=O
>>>
>>>
>>> WARNING 24 [file ADP.itp, line 53]:
>>>     Overriding atomtype C=O
>>>
>>>
>>> WARNING 25 [file ADP.itp, line 54]:
>>>     Overriding atomtype N=C
>>>
>>>
>>> WARNING 26 [file ADP.itp, line 55]:
>>>     Overriding atomtype C=C
>>>
>>>
>>> WARNING 27 [file ADP.itp, line 56]:
>>>     Overriding atomtype PO4
>>>
>>>
>>> WARNING 28 [file ADP.itp, line 57]:
>>>     Overriding atomtype O2CM
>>>
>>>
>>> WARNING 29 [file ADP.itp, line 58]:
>>>     Overriding atomtype OR
>>>
>>>
>>> WARNING 30 [file ADP.itp, line 59]:
>>>     Overriding atomtype CR
>>>
>>>
>>> WARNING 31 [file ADP.itp, line 60]:
>>>     Overriding atomtype O=C
>>>
>>>
>>> WARNING 32 [file ADP.itp, line 61]:
>>>     Overriding atomtype HCMM
>>>
>>>
>>> WARNING 33 [file ADP.itp, line 62]:
>>>     Overriding atomtype HOCO
>>>
>>>
>>> WARNING 34 [file ADP.itp, line 63]:
>>>     Overriding atomtype HOR
>>>
>>>
>>> WARNING 35 [file ADP.itp, line 64]:
>>>     Overriding atomtype HOCC
>>>
>>> Generated 25425 of the 25425 non-bonded parameter combinations
>>> Generating 1-4 interactions: fudge = 1
>>> Generated 22285 of the 25425 1-4 parameter combinations
>>>
>>> -------------------------------------------------------
>>> Program grompp, VERSION 4.5.3
>>> Source code file: toppush.c, line: 1071
>>>
>>> Fatal error:
>>> Atoms in the .top are not numbered consecutively from 1 (rather, atomnr
>>> =
>>> 1, while at->nr = 40)
>>>
>>> I know that the problem is related to the merging of 4 itp files.
>>> Please let me how I should do that.
>>>
>>
>> The ligands probably use common atom types and each .itp file likely has
>> an
>> [atomtypes] directive that introduces these new types.  Probably the
>> easiest
>> thing to do is create a merged [atomtypes] directive that lists all of the
>> necessary atom types so you don't list them separately in each file.  One
>> approach that I have used in the past is to create an .itp file that only
>> has
>> atom types in it, then call something like:
>>
>> #include "charmm27.ff/forcefield.itp"
>>
>> ; only has [atomtypes]
>> #include "my_ligand_atomtypes.itp"
>>
>> ; these don't introduce [atomtypes] any more
>> #include "ligand1.itp"
>> #include "ligand2.itp"
>>
>> -Justin
> But according to SWISSPARAM website I can only add one ligand.itp file.

Just a guess, but it's probably because each ligand.itp file introduces new atom 
types which give the conflicts above.

> So, is it possible to add ligand1 and ligand2 itp files?
>

Sure, my method should work.  Please try it.  I have done the exact same thing 
with Amber topologies from acpype.

> Will it be ok if I merge all the ligand pdbs and then get the combined itp
> file using that from SWISSPARAM and follow the protocol for one ligand?
>

Merging the coordinate files will probably not work.  If you have multiple 
molecules, you need multiple topologies.

-Justin

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

Justin A. Lemkul, Ph.D.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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