Dear Jason,
Thanks a lot for your quick response, what I am trying to do is the following:
I have two different ligands that are co-administered to patients, I want to learn about their mutual interaction or preferences in solution, to see if we can say something about the best way to do so (crystallization, nano-particles, etc.), so I did several simulations using just two copies of the ligands in water, but they just seem to escape each other during the simulation....
I have actually three systems in one: A+A, A+B or B+B, A and B being the two different molecules I have.
Thus I thought that calculating their interaction or free energy I would learn more about their mutual preferences. The truth is that I don't know how to this, since using ab-initio methods is very costly here.
If anybody has any suggestion how to study the interactions of two drugs in solution (or not) with amber, I would be very grateful.
Best,
Fabian Glaser
Technion, Israel
On Apr 24, 2014, at 2:38 PM, Jason Swails <jason.swails.gmail.com> wrote:
> On Thu, 2014-04-24 at 13:46 +0300, Fabian Glaser wrote:
>> Hi,
>>
>> I am interested to calculate the free energy of interaction on many frames of MD for two drug like molecules, I plan the following:
>>
>> 1) Prepare the molecules with antechamber
>
> OK.
>
>> 2) Run MD in vacuum
>
> Don't do this.
>
>> or water
>
> Do this instead.
>
>> 3) Calculate MM-PBSA as you did for a protein-ligand on http://ambermd.org/tutorials/advanced/tutorial3/
>>
>> Is that a good idea for two copies of drug molecules (e.g. RITONAVIR)?
>> Is the correct approach?
>> Is there any paper on that? I did not found any, but I am not an expert in the matter.
>>
>> Please note there is no protein involved here.... only two ligands.
>
> MM/PBSA will be of little use to you. An "interaction free energy" is
> difficult to compute using just energies (and don't forget, their
> interactions are strongly water-mediated so a simple pairwise summation
> between the molecules is unlikely to yield much insight).
>
> You can generate a general PMF using a radial distribution function, but
> I'm not sure exactly what you are trying to accomplish. Also don't
> forget that your free energy depends on your state (that is, the
> concentrations of each species), so it's important to specify what you
> want as specifically as possible (rather than just say "an interaction
> free energy"). It'll be easier to design an experiment or metric to
> measure what you want that way.
>
> Good luck,
> Jason
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
>
>
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_______________________________
Fabian Glaser, PhD
Head of the Structural Bioinformatics section
Bioinformatics Knowledge Unit - BKU
The Lorry I. Lokey Interdisciplinary
Center for Life Sciences and Engineering
Technion - Israel Institute of Technology
Haifa 32000, ISRAEL
fglaser.technion.ac.il
Tel: +972 4 8293701
Fax: +972 4 8225153
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Received on Thu Apr 24 2014 - 05:00:04 PDT
