I want to dock 2 ligands on a single protein. the ligands have different binding sites. while defining the input parameters- how to define the parameters for both the ligands? parameters for protein have been defined separately for the two different ligands/molecules.
What kind of parameters are you referring to?
If I understands correctly you want to perform a 3 body docking: 1 protein and two ligands.
The passive and active residues along with the interaction partner needs to be input for each of the three molecules.
So for protein(molecule 1)
There are two selections-
One for the binding site of molecule 2- they become the active n passive residues, with the interacting partner being 2.
Second- binding site for molecule 3(residues involved) becomes the active/passive residues with the interaction partner set as 3.
Now for molecule 2 n 3, what will these parameters be?
Because the program doesn’t accept the following:
Molecule 2 and 3- entire molecule interacts with the protein n each other- so the all residues are set as active/passive with interacting partners being 1,3 and 1,2 respectively.
Ideally you should define manually your interaction restraints (e.g. using http://alcazar.science.uu.nl/services/GenTBL/) and upload those as ambiguous distance restraints.
The 2.4 server however allows to you to define with which molecule one molecule interacts (in the input parameter tab).
For each molecule there is a Partner selections form.
In you case assuming you have two binding sites defined on your protein, each targeted by one ligand, the partner selections could look like:
1 -> 2,3
2 -> 1
3 -> 1
Each ligand should be defined as active.
But if the binding sites are separate, you can also simply perform two independent docking runs.
And for small molecule docking settings, check the following tutorial:
The thing is that i want to see the difference in the binding energies when i dock molecule 3 along with molecule 2 as compared to molecule 3 docked alone on my protein.