[gmx-users] Ligand during GPRC-membrane simulation

[Justin A. Lemkul]

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 the
> receptor but that is not the biological answer. 

If your system is not behaving in the biologically-dictated manner, I would 
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 they 
validated?

> 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 the 
moleculetypes, and again, if you're trying too hard to force something to 
happen, I would seriously question the accuracy of what you're doing.

> 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
> the end the ligand was completely out of the site.
> 

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

-Justin

> Could anyone help me?
> 
> Thank you in advance 
> 
> Sabine
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-- 
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Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
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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