Maybe yes, maybe not. Docking and visual inspection are not reliable indicators of the inhibitory potency. If, for some reasons, you really like this compound, just make it and test in an enzymatic assay (I don't mean you have to it yourself; you certainly have competent collaborators who would).

Dear Shamu,

You can't come to an conclusion Weather your compound is good inhibitor or not based on docking studies only... You need to perform wetlab experiments like enzymatic assays.. characterization...etc.. all the very best..

According to docking estimations yes it is a matter of steric interactions and your compound maybe can’t bind in a favorable way that means that you will have no action. But docking is a prediction program you have to do experimentals in vitro to come to a conclusion. Any way it is probably to be in accordance to docking studies.

Unfavorable interaction in molecular docking does not necessarily mean that compound is not a good inhibitor for many reasons including following:

1) protein flexibility is not taken into account in a commonly used docking protocols, so compound might fit due to induced fit effect (to overcome this problem, docking to several protein conformations or induced fit docking can be used),

2) the "right" binding mode of inhibitor might not be returned by the docking program (for example due to insufficient conformational sampling) or not top-scored by the used scoring function (re-scoring sometimes helps), so you might be analyzing a non-relevant binding mode,

3) other effects poorly accounted for in docking might play crucial role in activity (solvent, entropy, target interaction partners),

4) compound might have an unexpected mode of action or a different binding site.

Actually, it depends with different factors mainly depending with the sotware that you use for docking, we have several softwares, paid or free open source, differents algoritms also, flexibility of receptor (all receptor or just few aminoacids of active site). You should reparametrize your docking and re-run it several runs (until 50 or 100 run) to get a good results.

I agree with Jelena. The main problem is if the interaction is entropic driven, the score function likely will identify this ligand as a poor inhibitor.

To add one more aspect:

You could try solvated (hydrated) docking to have a more relevant binding pose of your ligand against your target of interest (ex. DNA or protein). You can try this option if the water molecules surronding your receptor have importance in terms of binding of the ligand to the 'active site'.