Positive energy contribution of Mg2+ ions in the binding energy of Protein-Ligand-Mg2+ ion

[gagandeep singh]

Hi All,

I am working on a protein which is known to have an ATPase activity but the exact site is not known. I ran a simulation of the protein with ATP and Mg2+ ions. The complex is very stable. On calculating the MMGBSA binding free energy of ATP with Protein-Mg2+, I got negative values for surrounding residues of protein (as expected) but the Mg2+ ion showed positive values (though I was expecting negative values here as well as a matter of stability). I ran the simulation with AMPPNP with protein-Mg2+ and got the similar results. 

I wanted to know if any additional parameters are needed to be added in input file while calculating MMGBSA energies in case of metal ions with protein and ligand complexes? 

Does gmx_MMPBSA tool had suitable parameters/compatibility for such simulations?

Looking forward to hearing from you.

Best regards,

Gagandeep Singh,
Assistant Research Officer (Biotechnology)
CARI,Jhansi, CCRAS, Ministry of AYUSH,
Government of India

[Mario Sergio Valdes]

In general, energy calculations based on MM for ions tend to be unreliable since a large formal charge is assigned (probably 2+ for Mg). In practice, there is charge transfer between the ion and the residues interacting with it, so it may be smaller. Facing an ion with a 2+ charge in the surrounding polar environment can make the electrostatic contribution considerably high and unfavorable. In this case, it is difficult to know what happens because no information is provided. To get a better perspective, please attach the energy decomposition graph of Mg, the surrounding residues, the ligand, and any other elements that provide information.

[gagandeep singh]

Dear Mario Sergio Valdes,

My apologies for the late response. PFA the per residue TDC and enthalpic energies images for ATP-MG-Protein and AMPPNP-MG-Protein complexes. Looking forward for your expert opinion.

Best regards,

Gagan

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Assistant Research Officer (Biotechnology)

Central Ayurveda Research Institute, Jhansi

Ph.D. Scholar

KSBS, IIT Delhi

Mob- 8178163366, 8285477478

[Mario Sergio Valdes]

Please attach the Mg energy components (Localize the Mg in the list of TDC residues and click the bar chart icon) to check it.