Good morning,
If you include both ligands in the tiregion you will get one single DV/DL. If you want to get separate ones I only see that you would have to run each ligand separately. Maybe TI component analysis is possible to get a DV/DL for individual ligands (see manual).
Anyway, the question is what you expect to get with this. You may see a difference in the initial MD simulation but keep in mind that a ligand can have more than one pose/binding mode an that's all you may see here. If your dimer is a homo-dimer, is there any reason to believe that on average, in an infinite simulation, the two ligands would show different binding free energies? As far as I understand, you have performed the simulation in solution. If the membrane is capable of introducing an asymetry in your case, I don't know.
Cheers,
Hannes.
________________________________________
From: carmine marco morgillo [FnTcy.hotmail.it]
Sent: 07 June 2017 17:44
To: amber.ambermd.org
Subject: [AMBER] TI in dimeric enzyme
Dear Amber list,
I am using thermodynamic integration (TI) on a dimeric enzyme embedded in membrane.
I have loaded each monomer with one ligand in a 1:1 ratio and produced classical molecular dynamic simulation. After 150 ns I have analyzed the binding modes in each monomer and I have noticed some differences in the orientation of the ligands. Then, I would like to perform TI to transform my ligand (A) in a similar one (B) in order to predict the relative binding energy in each monomer.
On the same system without membrane, I used one-step softcore potential TI method performing alchemical transformation in one monomer at a time and choosing 9 windows of 5 ns for the coupling parameter (lambda). However, this time the membrane should be taken into account due to the proximity to the binding site of the ligand. Therefore, due to the dimensions of my system (dimer + ligands + membrane + water = 230000 atoms) I wonder whether is possible to build the system in a way that the transformation from ligand A to B occurs in both monomers, so I could derive separately DV/DL values on each ligand per monomer.
I am using Amber 14.
Any suggestion is appreciated.
Ciao,
Carmine
******************************
Carmine Marco Morgillo, PhD
Dipartimento di Farmacia
Facoltà di Farmacia
Università di Napoli "Federico II"
Via D. Montesano, 49
80131 Napoli
fntcy.hotmail.it<mailto:fntcy.hotmail.it>
carminemarco.morgillo.unina.it
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Received on Thu Jun 08 2017 - 01:00:03 PDT
