Further complications arose when running funnel metadynamics simulations of the coiledcoil trimer CC-Tri. Similarly to the funnel metadynamics simulations of CC-Di and apCC-Di, the representative bound states did not resemble the desired native coiled-coil structures (Figure ). This is supported by inspecting the inter-helical interactions formed between helix A ('ligand') and helices B and C ('receptor'), where multiple undesired contacts can be seen (Figure ). Additionally, the inter-helical interactions between helices B and C revealed that the 'receptor' is re-arranging in the absence of the 'ligand', forming a coiledcoil dimer, with salt bridges on both sides of the complex. This is in contrast with the salt bridges expected on the 'receptor', which should form only on one face of the complex (Figure ). This introduced two further complications to the calculations. Firstly, helix