[gmx-users] Re: question about free energy. Gromacs user

[Maik Goette]

Because you are quite greedy with parameters, one can just rougly assume 
that,e.g. your distance restraints are too short and therefore just kind 
of bend your ligand. Therefore it seems to find an energy minimum in 
modifiying some internal degrees of freedom to your restraint potential.
Maybe you have to apply simply more distance restraints along the whole 
ligand. Maybe you should stick to methods like TI or pulling, which are 
implemented and heavily used within GROMACS...

Regards

Maik Goette, Dipl. Biol.
Max Planck Institute for Biophysical Chemistry
Theoretical & computational biophysics department
Am Fassberg 11
37077 Goettingen
Germany
Tel.  : ++49 551 201 2310
Fax   : ++49 551 201 2302
Email : mgoette[at]mpi-bpc.mpg.de
         mgoette2[at]gwdg.de
WWW   : http://www.mpibpc.gwdg.de/groups/grubmueller/


bmmothan at ucalgary.ca wrote:
> Thank you David and Arneh for the comments.
> 
> I just have a couple of things i want to clarify about the constrain
> distances i used.  The distance I used to pull the ligand and receptor
> apart was a non-bonded distance between the amide nitrogen of the ligand
> and the oxygen carbonyl of the receptor (on both ends).  looking at the
> slowgrowth results of my 5 ns, the distances i specifed increased from
> lambda 0 to 1, however, I didnt get separation as I wanted it since the
> ends just separated and the middle interaction of the ligand-receptor
> stayed intact. nothing unusal happened to the ligand or receptor.
> I dont think my method altered the internal degrees of freedom of the
> ligand. Can you please clarify this issue for me.
> 
> I used constraint=all-bonds in my mdp file.
> 
> Again, thanks you both for the comments.
> 
> Belquis
> 
> 
> 
>>> Maybe it should be obvious, but (a) why are you constraining two
>>> distances, and (b) are you sure your constraints aren't going to muck
>>> with the internal degrees of freedom for the ligand? I would think one
>>> would like to pull the ligand out of the receptor along some
>>> particular direction, but without doing anything to alter its internal
>>> degrees of freedom, or there would be a free energy associated with
>>> changing its internal degrees of freedom that you wouldn't capture in
>>> the PMF calculation.
>>>
>> I agree with David's comments here.  Check out the 'Special Topic'
>> section
>> of the GMX manual.   you can either do a pulling simulation or umbrella
>> sampling (where the position and constrain the ligand on some rxn
>> coordinate, in several simulation).  The output of such simulatsions is a
>> *.pdo file, which you can then run g_wham on to obtain a PMF.
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> 
> 
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