My query could be trival.I have docked an ihhibitor-protein complex and defined the active site of the protein. Ligand was placed roughly at the active site for the docking .After analyzing the out put files the hydrogen bonds were not being formed at the active site residues but with the residues other than in the active sites.I need to carry out the MD study for the same. Can i go ahead???
You can go for dynamics but it is better if you look for the pose that is having the essential interactions (proved experimentally).
In case you don't have, you can go, as forming hydrogen bonds with the receptor is counted as one of the factor causing inhibition.
It is very unlikely (though not impossible) that a true pose for a true active does not feature any hydrogen bonds.
What if the the amino acid residues that do not belong to the active site actually do belong to the active site?
It might possible that the residue which involved in hydrogen bond interactions belongs to active site.
You can get the answer to your question until and unless you run the MD simulations.
Another way is to treat few active site residues flexible to see whether the residues of your interest is involved in any interactions or not.
Along with what others have suggested I would like to add, mutating the amino acid which is forming the hydrogen bond and then checking its effect on docking energy.
And if your active site residues definition is based on experimental data then I think dynamics can help you to explore the residence time of that particular hydrogen bond. Which could ultimately help you in inferring the importance of the aforementioned hydrogen bond.
Thank you all for your valuable comments.The active site defined is the experimentally proven one !!!
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