Hi everyone,
I am doing MMGBSA and RMSF analysis of binding of two ligands (ligand1
and ligand2) to a protein at 2 sites (site 1 and site 2).
The idea is to see the effect replacement of one ligand (say ligand1) at
site 1 with ligand2 to the binding of ligand1 at site2.
So i ran two MDs (MD1 and MD2).
First one consisted of ligand1 at both sites and the second having
ligand2 at site1 and ligand1 at site 2.
I ran the system for 350ns.
After MMGBSA i found there is decrease in affinity of ligand1 to site 2
upon replacement of ligand1 with ligand2 at site1.
the enthalpic and entropic contributions at site 2 changed as follows (the
ligand at this site has remained same, changes are due to replacement of
ligand at the other site)
MD1 MD2
Enthalpic -45.51 --> -43.84
Entropic(TDeltaS) -36.56 --> -38.42
Total -8.95 --> -5.43 kcal/mol
The enthalpic term is ok as it is increasing hence the decrease in final
binding affinity.
Issue is with entrpoic term.
From RMSF analysis of protein i know there is increase in RMSD of almost
every residue in the protein (including active site residues) hence i
believe there is increase in entropy overall.
It also seems ok to think this increase in entropy will lead to decrease
in binding affinity.
But entropic value in MM GBSA analysis goes from -36.56 to -38.42 i.e. a
net decrease in value. Does this mean entropy is decreasing according to
MMGBSA?
Or does increase in entropy lead to a more negative value of TDeltaS?
I am a bit confused. I am ready to elaborate if the question is not
clear.
Regards
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Received on Wed Jun 14 2017 - 05:00:02 PDT
