You would need to perform docking studies with the separate isomers.

Dear Mr. Karpe,

Yes. You need to perform docking studies with the separate isomers of your interest. But I recommend you to minimize your molecules (separate isomers) by QM calculation prior to molecular docking. It will give more accurate results.

Thanks

Best wishes,

Sk. Abdul Amin

thanks to all for valuable suggestions.

As above - do the docking with separate (dia)stereoisomers. You might also want to look at your tautomer state, if this is relevant (start with the most stable tautomer), and if you have acids and bases in the molecule, consider protonation state at relevant pH (ie. the pH used in the assay, likely).

Minimising your structure with QM - not so sure. QM generally reflects an in-vacuo system. Docking methods typically use forcefields, which try and predict conformations in solvent (water). Minimisation in a forcefield similar to that used by the docking should be ok (OPLS for Glide, OPLS or MMFF for GOLD etc. should do).

Absolutely yes. A pair of enantiomers represents two different compounds which may assume different orientation into binding site. You must compare poses of both enantiomers for essential interaction as compared go the reference compound you are using. Autodock, GOLD etc. programs are good. Either way around you can compare minimized as well as non-minimized conformations of isomer also. You can check the type of interactions addressed by individual force fields, i.e., H-bond, pi-pi interactions, metal chelation, hydrophobic interaction etc. and decide which forcefield to use.