[gmx-users] Constrains and TI

Maik Goette mgoette at mpi-bpc.mpg.de
Wed Aug 8 10:37:28 CEST 2007


First, for the other topic you posted (which is probably somehow related 
to this one):

Now, please be more specific with what you want to do....You wrote:
"What I want to do is calculate the free energy difference of pulling 
the ligand away from the receptor"

This is a pulling approach, where you would like to do AFM sims and 
afterwards use Jarzynski. If that is what you want, search the 
literature for Jarzynski and try to understand his theorem (you will 
see, one pulling sim is not enough for free energy calc).

Then you wrote:
"I want to do it using theromdynamic intergration using the Lamda 0/1 stuff"

This is a totally different approach....

With both, you can ESTIMATE binding free energies. Still, both are very 
different in the way to setup a simulation in GROMACS. You WILL find 
out, how to do it by:
1. Reading the manual
2. Searching the mailing list
3. Using the GROMACS Wiki
4. Using some of the tutorials, which were posted, by e.g. David Mobley

Now, coming to your idea about using distance restraints to "pull" the 
ligand away (its more of a push).
I think (correct me if I'm wrong), that you can't use A and B state 
distance restraints in GROMACS (or better say, they will stay the same 
for both states).

I'd suggest to use either TI OR AFM pulling. For sure, you could do both 
and see, if you get similar free energy differences with both methods...
I don't think, you can calculate the free energy difference by using 
different distance restraints, anyway.


As I just saw it. Inform yourself about the difference between 
CONSTRAINTS and RESTRAINTS (there is an important one...)

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

bmmothan at ucalgary.ca wrote:
> hello all,
> is it possible to constrain a distance (or several) between a
> ligand-receptor complex inorder to simulate free energy change of
> separating the ligand from the receptor?
> I intend to use TI and lamda to do free energy calculations.
> any help is appreicated.
> Belquis
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