I am going to perform ligand-protein docking with HADDOCK.I have 5 lysine amino acids that need to be flexible in order for my ligand bind in since they otherwise would sterically hinder the ligand. However, I don´t know if all of the lysins are interacting with the ligand via electrostatic interactions. My question is if the lysins should be set as active residues in order to obtain flexibility or if they need to be interacting with the ligand to be classified as active residues?
Hi Leo
The flexibility is only introduced in the refinement stage. So if your lysine side-chains are preventing entry you need to deal with those before.
My advice would be to first sample different side-chain conformations before docking and give an ensemble of conformations to HADDOCK.
Further if you need to reach a buried site, you can decrease in the intermolecular energy to allow the ligand to penetrate the binding site (the inter_rigid parameter).
Refer also to our online protein-ligand docking tutorial for ligand-specific settings. See: