Hi,

In my opinion, to address your question two major aspects may be considered:

Chem B. 2013 Jul 18;117(28):8408-21.

Further, you might want to have a look at a recent paper cited below. This paper may be useful in providing some insights in using the mm/GBSA binding affinities for direct comparison and interpretation.

Godschalk F, Genheden S, Söderhjelm P, Ryde U. Comparison of MM/GBSA

calculations based on explicit and implicit solvent simulations. Phys Chem Chem

Phys. 2013 May 28;15(20):7731-9. doi: 10.1039/c3cp00116d

HTH!

Hi

You can justify your energy values by comparing protein-ligand interaction for both the protein.

Hi,

In my opinion, to address your question two major aspects may be considered:

Chem B. 2013 Jul 18;117(28):8408-21.

Further, you might want to have a look at a recent paper cited below. This paper may be useful in providing some insights in using the mm/GBSA binding affinities for direct comparison and interpretation.

Godschalk F, Genheden S, Söderhjelm P, Ryde U. Comparison of MM/GBSA

calculations based on explicit and implicit solvent simulations. Phys Chem Chem

Phys. 2013 May 28;15(20):7731-9. doi: 10.1039/c3cp00116d

HTH!

There is nothing fundamentally wrong with this comparison, but you might want a few more controls before drawing any conclusions.  The energy difference of 20 kcal/mol is large, but then, so are your total energies, obviously much much larger than any real binding would ever be.  This may simply be due to limitations in the forcefield, but it may also indicate that you have not reached the true equilibrium and/or that you have not sampled enough for the entropy portion of the calculation to converge properly.  

I would recommend two things:

1) You mention a positive control you used with the compound with known selectivity, but it would also be useful to use something known not to bind to get an idea of how your MM/GBSA is performing

2) Double all the simulation times and see how much your results change.   Or, run a second simulation for each condition, starting from a slightly different set of starting coordinates and using a different random seed for langevin dynamics and ensure that the results from this second set of simulations give the same results as the first.