DELTAS: Total Energy Decomposition of metal ions

[Martin Bonin]

Hey everybody,

I ran a lot of mmpbsa calculations for my simulations including the decomposition analysis. My enzyme contains a metal ions, which is exposed on the surface. For the DELTAS: Total Energy Decomposition, the metal ion has a highly negative (-65) electrostatic and an even higher positive (+111) polar solvation value leading to a positive value in total and thus, a negative contribution of the metal ion for the substrate binding, right? How can I interpret these values?

So from my understanding, the electrostatic value is so low, because I have a strong electrostatic interaction with my substrate. However, the high polar solvation value suggest that the metal ion prefers to be surrounded by water molecules instead of the substrate.

Is that correct?

Thank you very much in advance

Best regards

Martin

[marioe911116]

Hi Martin! thanks for using gmx_MMPBSA... Although your results seem reasonable, I will be careful when interpreting absolute values coming from MMGBSA calcualtions. I would rather prefer working wiht relative values, that way the errors will cancel and the results will be more feasible. I reccomend to read this puclication (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570792/) to get a better idea how to assess the polar-desolvation penalty of the solute molecules (ΔG ds) and the screened electrostatic energy variation (ΔGscel) upon complex formation...

hope this helps!

Mario

[Martin Bonin]

Hey Mario,

thanks for the quick reply and thanks for the paper suggestion. It took me a while to read and I certainly did not understand everything, but this is a really interesting paper. However, I'm not sure if I got what you mean with relative values. I know, that the values calculated by MMGBSA can not be expected to give an exact result. But from my understanding, I can use it for example to compare the binding energy of different substrates with my enzyme. And I can check which residues show a different contribution to the binding energy and thus, might be responsible for the difference I see in the total binding energy (DELTA TOTAL) of the different substrates. So by relative values, do you mean this comparison of for example different substrates?

Best regards

Martin

[marioe911116]

Exactly... MMGBSA gives you better estimates when comparing several ligands rather than focusing on the absolute values for one of them... The paper I sent around is a little bit large... I suggest you to go and check the "Calculation of polar-desolvation and screened electrostatic energies" in Material and Methods section.

hope this helps!