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 Wed Jun 07 2017 - 10:00:04 PDT
