I have calculated the BE of a small ligand (mol wt ~320 g/mol) with its receptor. The BE I have obtained was ~670 kJ/mol (~160 kcal/mol). I am little afraid of such a high value for the BE. Is it possible to get such a high binding energy for this small ligands? I am worried whether the results are right or wrong in publication point of view. I do not have in vivo experience for BE calculation that differ significantly from in silico where we do not consider the entropy contributions.
The APBS program calculate only the electrostatic component of the binding energy of protein-ligand: that is change in the desolvation energy upon binding, which is the change in complex-solvent and ligand-solvent, protein-solvent electrostatic interaction energy, and protein-ligand electrostatic interaction energy change upon binding. So, it does not include reorganization energy of the solvent, which captures by the SASA term (energy to create a cavity of the size of solute in solvent) and change of the vdw-energy upon binding, change of internal energy upon binding, and of course the entropic term. I think, these last terms may influence the values you are getting.
I am giving a link to the AMBER tutorials in MM_PBSA technique that is related to what you are doing, it is easy to find many papers written on this technique.
http://sf.anu.edu.au/~vvv900/amber-tutorial/1cgh-ligand/mm-pbsa.html
Thank you very much Dr. Hiqmet Kamberaj. The problem am facing is the large difference in the binding free energy, Initially I calculated the BE for Prot-ligand taking 500 (PDB files) snapshots from the Gromacs MD trajectory. The score was -15.5 kJ/mol. Now when I wanted to perform alanine scanning of single amino acids (8 different residues), I got some structural error during minimization. So I changed the PDB files to GRO files and successively calculated BE for each mutated case. But the score I got was -670kJ/mol. Which seems wrong. For a single mutation the difference value should not be so large. So kindly help me where is the problem. Why in PDB file calculations the BE = -15 and in GRO it is -670kJ/mol. Hoping apositive response.
Thanking You
Sincerely
Bikash
How you are calculating BE? A outline will be helpful to trace the origin of error. I guess, if a residue is mutated, topology of molecule has to be changed. A pqr file is required as input for the APBS, so how you are converting a gro file to pqr file?
Entropy: A concept that is not a physical quantity
https://www.researchgate.net/publication/230554936_Entropy_A_concept_that_is_not_a_physical_quantity
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