That sounds more reasonable...:)
In fact I like the idea of using distance restraints, but I still doubt,
that will work...
I would really suggest to use the TI method. If you apply it properly it
should give reasonable results. With proper application, speaking about
using soft-core for VdW (with good parameters), hardcore for qq, back
and forth morphing for an idea of the hysteresis or using discrete TI
instead of slow-growth, etc. you should get reasonable results. But
depending on your perturbation size this could also be a hard task, to
obtain correct numbers and not just building the famous costly random
number generator...
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/
[EMAIL PROTECTED] wrote:
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
ligand/receptor complex.
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
free-energy code)
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
receptor.
please correct me if I am wrong.
and thanks for ur help.
Belquis
Hi
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.
Regards
P.S.
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
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/
[EMAIL PROTECTED] 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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