[gmx-users] RE: gmx-users Digest, Vol 66, Issue 124

Thielges, Sabine Sabine.Thielges at cnrc-nrc.gc.ca
Mon Oct 19 18:40:45 CEST 2009

Thielges, Sabine wrote:
>> Hi everyone,
>> I am currently doing a simulation which involves a dopamine receptor 
>> placed in a POPC membrane and an agonist or antagonist in the active 
>> site. The ligand was placed by VS and is closed to what the biology 
>> gives. My problem is that the ligand get out of is normal position 
>> during the simulation. I know it is easier to move the ligand than
>> receptor but that is not the biological answer.

>If your system is not behaving in the biologically-dictated manner, I
>guess that whatever parameters you are using are unsuitable.  Which
force field 
>are you using, and where did you get the ligand parameters?  How were

I am using the force field ffG53a6 for both, it was the one recommended
by the membrane tutorial.  the ligand parameters were created using the
web site PRODRG which generates a drggmx.itp type that I have to
manually modify since all the atoms types are not in the protein ff that
I am using. Not the best but I didn't know which other ff would be
appropriate for both receptor and ligand.

>> I would like to know if there is a way to fix the ligand so that the 
>> receptor would be force to adapt around it and not the inverse. There

>> is know Hbonds with specific amino acid is it possible to add this 
>> information in the run.

>You could implement distance restraints, but that would require merging
>moleculetypes, and again, if you're trying too hard to force something
>Happen, I would seriously question the accuracy of what you're doing.

I have the same doubted, but I know for the receptor it self I had to do
the same thing. I added position restraints that I gradually decreased
from 1000 to 0 by doing few small MD and then I could do the real MD
without any. My idea was to find a way to do the same thing with the
drug nut I couldn't find any.

How can I merge the 2 molecules since my ligand is not a protein and
pdb2gmx doesn't work when I have it in my structure.pdb?

>> I tried so far to use position restraint in my ligand.itp
>> [ position_restraints ]
>> ;  i funct       fcx        fcy        fcz
>>    1    1       10000      10000      10000
>>    3    1       10000      10000      10000
>>    4    1       10000      10000      10000
>>    5    1       10000      10000      10000
>>    6    1       10000      10000      10000
>>    8    1       10000      10000      10000
>>    9    1       10000      10000      10000
>>   10    1       10000      10000      10000
>>   11    1       10000      10000      10000
>>   12    1       10000      10000      10000
>>   13    1       10000      10000      10000
>>But it didn't have any effect on the final MD simulation of 10 ns. At 
>>he end the ligand was completely out of the site.

>Then you didn't actually apply position restraints.  Did you use
>define" statements in the .mdp file (if necessary)?

I know that I don't because if I create a posre.itp for the drug like I
do for the receptor and that I define it in my .mdp, I got a message
error saying that I define atoms in the wrong molecule. Because the
ligand is not the protein.

Thanks again for your help.


> Could anyone help me?
> Thank you in advance
> Sabine
> ========================================

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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