I am refining a tetrameric protein which has ligand placed at the center axis. There is one tetramer in ASU.  I added the ligand with 0.25 occupancy and performed the refinement using both phenix and refmac. Refinement leaves lots of green density around the ligand inferring that there may be four different conformation of the ligand. When i made four different conformation of ligand (each with 0.25 occupancy) and started refinement, there is lot of clashes in ligand itself. Is there a ways to refine the four different conformation of ligand with different conformation with 0.25 occupancy avoiding clashes in ligands?