Dear researchers,
I ran 250 ns MD simulation of estrogen receptor alpha-tamoxifen complex through Gromacs 2019 package using amber99sb-ildn.ff. Now, I am trying to calculate the binding energy with G_MMPBSA tool. As my binding packet is a hydrophobic site, I took solute dielectric constant value 2. But in that case, I am getting the electrostatic energy very high in negative value (-680.105 +/- 127.917 kJ/mol). When I tried with solute dielectric constant value 4, then I am getting electrostatic energy -170.026 +/- 31.979 kJ/mol. I am sharing the two calculation summary below:-
Solute dielectric constant value 2
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SUMMARY
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van der Waal energy = -216.060 +/- 14.275 kJ/mol
Electrostattic energy = -680.105 +/- 127.917 kJ/mol
Polar solvation energy = 266.276 +/- 79.672 kJ/mol
SASA energy = -22.645 +/- 0.817 kJ/mol
SAV energy = 0.000 +/- 0.000 kJ/mol
WCA energy = 0.000 +/- 0.000 kJ/mol
Binding energy = -652.534 +/- 57.484 kJ/mol
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END
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Solute dielectric constant value 4
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SUMMARY
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van der Waal energy = -216.060 +/- 14.275 kJ/mol
Electrostattic energy = -170.026 +/- 31.979 kJ/mol
Polar solvation energy = 223.137 +/- 62.078 kJ/mol
SASA energy = -22.645 +/- 0.817 kJ/mol
SAV energy = 0.000 +/- 0.000 kJ/mol
WCA energy = 0.000 +/- 0.000 kJ/mol
Binding energy = -185.595 +/- 28.806 kJ/mol
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END
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Kindly help me to determine the correct solute dielectric constant for my system. I am also attaching the 2D receptor-ligand interaction plot for this purpose.
Hi, I thought Solute dielectric constant value 4 should be better for your system seen from the value. In the "g_mmpbsa" paper , the author also tested different solute dielectric constant (2 and 8), in his system, the better result is 2.
Ranabir Majumder check gmx_MMPBSA, a new tool aid to perform end-state free energy calculations with GROMACS files. Things you can do with gmx_MMPBSA:
-binding free energy with different solvation models (PB, GB, or MM/3D-RISM) which should be good in your case
-stability
-alanine scanning
-entropy corrections
-binding free energy decomposition
gmx_MMPBSA has been written in Python3.8 and is entirely based on AMBER’s MMPBSA.py, a widely used tool for streamlining end-state free energy calculations. The program is freely available (test files and tutorials included) at https://github.com/Valdes-Tresanco-MS/gmx_MMPBSA
hth!
The solute dielectric constant can be applied within a range of numbers in which the authors had demonstrated in their study and -pdie 2 was found significant. However it worth nothing that your protein differs from theirs. For highly charged solute high dielectric value will produce more accurate polar solvation energy. However the dielectric constant for solute equal to 4 is appreciable small. Thus using 4 instead of 2 may be more efficient in this case. This corroborates the docking pose
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