I'm currently using Vina to and comparing the docking results from antagonists and agonists of a receptor. The docking of the agonists works just fine, but the antagonists are not docked in useful poses. This is weird, since the original receptor structure has been crystallized with an antagonist bound. My suspision is that Vina disfavours larger molecules, antagonists for this receptor tend to be larger and have more flexible bonds as I can say from the analysis of the docks of my database.
Is there a way to tweak the scoring function to enable e.g. soft repulsion? Or scale the vdw radii? Maybe just increasing the exhaustiveness could do the trick (larger comformational space to sample?)?.
I'll appreciate any suggestions