Was the crystal structure of the protein-ligand complex obtained by co-crystallization or soaking?

Co-crystallization

Well, the H-bondings are the physical phenomenon and reflect the near actual orientation of the ligand as it would be at the site.

dear alamgir,

my advice:

1. Do not use blind docking, but use docking with a grid according to the position of the original ligand.

2. Generally, a good inhibitor is one that has a sufficient number of hydrogen bonds and other hydrophobic bonds

3. If you compare the test ligand with the native ligand, then the inhibitor properties can be seen from the similarity of the interaction between the test ligand and the native ligand with the residue.

Thanks for your kind suggestion. However, is it possible that the grid parameters are like this in case of blind docking?

it seems that the grid size is too large, covering the entire protein volume. try to reduce it (zooming out), until it reaches the binding site of the protein with native ligand.

Thanks, Dr. Komari for your suggestion.

It is not necessary that the poses of your docked ligands are the same as the co-crystallized ligand (especially when they are not chemically similar). Also keep in might that the highest docking results should be experimentally validated or you can conduct MD simulations to check the stability of the complexes.

Dear Sir,

Have you test your compound in vitro?

If I answer your question, hydrogen bonds and other hydrophobic interactions are very important for protein-ligand interactions but it does not mean that it determines molecules as a good binder or not. It is just one of the parameters which determine binding affinities for targeting sides. It can just say about its fitting to the binding pocket, just it. It may be also confusing in many cases for accurate evaluation, for instance, nucleic acid derivatives give good results about hydrogen bonding as they have active hydrogen binding sites, but others may not have. So, İ think, using just hydrogen bonding profiles for affinity comparison is not a good choice at all.

As is recommended above, you can change your grid-box for better results if you have to show its binding affinity on the experimental pocket and run MD simulations for the best. Also, it is likely that you will never be able to catch experimental results from your simulations too because it is the biggest concern for in-silico studies (contradiction between in-vitro and in-silico results).

**check your docking protocol as well..