[gmx-users] Constrains and TI
bmmothan at ucalgary.ca
bmmothan at ucalgary.ca
Wed Aug 8 19:38:41 CEST 2007
Thank you for the reply,
Sorry for the confusion of my two emails. I guess I was using the word
"pulling" in the wrong context. Now after my extensive reading, what I
meant is that i want to calculate the absoulte binding free energy of a
I have read the manual over and looked at the tutorials, and came to the
idea that i can constrain distances b/w the ligand and the receptor and
input a distance for state B to vary the distance using lamda. (Manual 3.3
chapter 6 special topics, section 6.3 Calcuating the PMF using the
I am using contraints type 2, which can be perturbed in free energy
calculations. here is what I used in my calculation:
[ constraints ]
; ai aj funct length_A length_B
44 258 2 0.259 2.406
123 179 2 0.329 2.334
I am currently running a 5ns using the slow-growth method to give me an
idea of what happens to the system.
I am also looking into using orientational-restrains and using a
thermodynamic cycle instead of PMF of the unbinding of the ligand to
please correct me if I am wrong.
and thanks for ur help.
> 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
> 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.
>> gmx-users mailing list gmx-users at gromacs.org
>> Please search the archive at http://www.gromacs.org/search before
>> Please don't post (un)subscribe requests to the list. Use the
>> www interface or send it to gmx-users-request at gromacs.org.
>> Can't post? Read http://www.gromacs.org/mailing_lists/users.php
> gmx-users mailing list gmx-users at gromacs.org
> Please search the archive at http://www.gromacs.org/search before
> Please don't post (un)subscribe requests to the list. Use the
> www interface or send it to gmx-users-request at gromacs.org.
> Can't post? Read http://www.gromacs.org/mailing_lists/users.php
More information about the gromacs.org_gmx-users