Input values for calculating van der waal and electrostatic energy

[Khushboo Singh]

Hi g_mmpbsa users!

I have calculated protein-ligand complex binding free energy using g_mmpbsa (for energy values see below and find the attachment for polar and apolar mdp files). The ligand binds to the hydrophobic pocket of the protein; the protein is negatively charged, while the ligand is neutral. The experimental binding energy is approx -40 kJ/mol. The experimental DGbind correlates with the binding energy calculated by linear interaction energy method, but the value obtained from MM-PBSA is way too high.

van der Waal energy = -366.265 +/- 0.000 kJ/mol
Electrostattic energy = -34.064 +/- 0.000 kJ/mol
Polar solvation energy = 149.893 +/- 0.000 kJ/mol
SASA energy = -25.881 +/- 0.000 kJ/mol
SAV energy = 0.000 +/- 0.000 kJ/mol
WCA energy = 134.669 +/- 0.000 kJ/mol
Binding energy = -141.645 +/- 0.000 kJ/mol

My questions are:

1. I am assuming that either my van der Waal (vdw) energy is overestimated or the electrostatic energy is underestimated. How could I change the input values since I did not use any mdp file to calculate vdw and electrostatic energy? I tried using -rvdw option to change the vdw radii but the values in the energy_MM.xvg file does not change at all. The command used:

g_mmpbsa -f test.xtc -s test.tpr -n index.ndx -pdie 2 -decomp -mm test.xvg -mmcon test.dat -rvdw 0.9

Also, what is the default value for rvdw? According to the tutorial, the value is 1nm, but the help command (g_mmpbsa -h) shows the value to be 0.1 nm.

2. I calculated the entropy contribution using g_covar and g_anaeig tool, which was around 37 kJ/K. The entropy is conformational entropy found by fitting a multidimensional harmonic potential to the multidimensional distribution of coordinates. Do I need to multiple this term with temperature (TS) before subtracting it from the overall binding energy?

It would be of great help if you could help me fix the energy values.

Thank you
Khushboo Singh
Ph.D. Candidate

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1. I am assuming that either my van der Waal (vdw) energy is overestimated or the electrostatic energy is underestimated. How could I change the input values since I did not use any mdp file to calculate vdw and electrostatic energy? I tried using -rvdw option to change the vdw radii but the values in the energy_MM.xvg file does not change at all. The command used:

MM/PBSA method overestimates the binding energy and several publications reported this result. You may look into g_mmpbsa and other referenced publications. 

 

g_mmpbsa -f test.xtc -s test.tpr -n index.ndx -pdie 2 -decomp -mm test.xvg -mmcon test.dat -rvdw 0.9

Also, what is the default value for rvdw? According to the tutorial, the value is 1nm, but the help command (g_mmpbsa -h) shows the value to be 0.1 nm.

-rvdw is used for atoms with missing van der Waals radius. It does not affect calculations if radius for atoms are already present in the library.

 

2. I calculated the entropy contribution using g_covar and g_anaeig tool, which was around 37 kJ/K. The entropy is conformational entropy found by fitting a multidimensional harmonic potential to the multidimensional distribution of coordinates. Do I need to multiple this term with temperature (TS) before subtracting it from the overall binding energy?

We do not know that the quasi-harmonic approach is compatible with MM/PBSA method, and therefore we cannot comment on this method.

g_anaeig calculates entropy, so it should be multiplied by Temperature before subtracting it from binding energy.  

[Khushboo Singh]

Thank you so much for your response.

Regards,

Khushboo Singh