I was wondering whether there is any limitation of the number of conformers for Rosetta Ligand docking. I have a large ligand with 25 rotatable bonds and generated top 500 conformers with BCL. The reason I picked 500 conformers is that I saw in Rosetta papers they worked with 100 conformers for a small molecule with around 5 rotatable bonds, so I thought I need to increase the number of conformers propothional to the number of rotatable bonds? Is this correct or do I need to include all the conformers? Moreover, should I change any parameters in Transform mover like the number of cycles due to the large conformers I have?
One more question: I read a paper stating that one should split the large ligand into fragments before parameter generation. I tried to do that but molefile_to_params.py failed to generate parameters. I am not sure whether that statement is still valid.
What extra steps I should follow when I work with large ligands in Rosetta ?
Any suggestion would be highly appreciated.