Gmx_MMPBSA binding energy

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1

I am doing protein ligand simulation, and after completing the simulation, I went for binding energy calculation using gmx_mmpbsa.

My simulation time was 500 ns, I calculated binding energy for my ligand and I got positive binding energy but when referred to similar work previously done in my lab it should have been negative.

I observed a strange thing when I added hydrogen using pymol in the ligand preparation step. I got positive binding energy (+12.345 kcal/mol) .

But for similar thing when I used Avogadro to add hydrogen to my ligand it gave me negative binding energy (-53.183 kcal/mol).

So does addition of hydrogen by different tools can actually have this much effect?

Please let me know your views on this, will be greatly helpful.

2

I don’t understand. I assume you added hydrogens before energy minimizing and running the MD simulations. As long as the force field parameters for the ligand are the same it should not matter how the hydrogens are added.

3

Yes, Hydrogens were added before energy minimization. When we are generating the ligand topology in that very same step before converting the .mol2 format. I used amber99sb force field and generated ligand topology using acpype.

4

So, you mean that you got two different topologies depending on if you added the hydrogens with Pymol or Avogadro?

5

I guess so, as the total atoms after adding hydrogen with Pymol were 120, whereas the total atoms were found to be 121 in case of Avogadro.

6

Then choose the tool that gives you the molecule that you are studying. Both cannot be correct.
Edit: It could of course be a matter of protonation state. Then choose the state that is expected at the relevant pH.

7

Makes sense, thank you for your time and input. Have a good day.