Dear All,
I have calculated binding free energy for my complex of ligand-receptor and its mutant form (one of the residues in ligand was mutated to ALA) using the MM-PBSA method (Perl version) implemented in AMBER. I ignored the contribution of entropy in the calculations. Because it is computationally and apart from this when comparison of binding energy is desired entropy can be neglected. It should be noted that separate MD simulation was performed for mutant and wild type using single trajectory approach. The force field used was Amber 99 force field.
The residue that I mutated to Ala, was Tyr and it has been proven experimentally that this residue is so important in interaction with receptor and it is one of hot spots in binding site of interaction by providing π-π stacking with phenyl alanine of receptor.
But when I mutated it to Ala and the binding energy was calculated, it was observed that the value of binding energy was smaller than wild type more likely to negative values than the wild type and accordingly resulted to that improved affinity toward receptor by this substitution in spite of our expectation that it is highly unfavourable substitution.
My question is that whether this discrepancy is related to the method and force field. Is aromatic π-π stacking interaction (phenyl-phenyl interaction) considered in the force field? Or it is as a result of ignoring the entropy.
Any help would be highly appreciated!
Thanks
Maryam
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Received on Tue Dec 28 2010 - 03:30:02 PST
