In the water case, it was observed that the bonds between atoms 4-5 and 5-6 were able to rotate fully during the simulations. However, in the complex environment with HIF2A, the behavior changed due to steric hindrance of the protein. No rotation of the ring was observed in any of the three replicates (See Figure ). This suggests that for the atom mapping generated by 2D Lomap and 3D Lomap for this ligand pair, the binding mode might be altered (see Figure ). In the simulated case, we found that the correct orientation was obtained on energy minimizing the system and therefore no change of the binding mode occurred luckily.