The remaining structures (competing topologies and oligomerisation states) were designed in ISAMBARD, employing parametric modelling. The competing topology struc-tures include an antiparallel variant of CC-Di, a parallel variant of apCC-Di and an updown-up variant of CC-Tri. The competing oligomerisation state structures include CC-Di designed as a parallel trimer and tetramer, CC-Tri designed as a parallel dimer and tetramer, and CC-Tet designed as a parallel dimer and trimer. CC-Di was also designed as a parallel dimer, to compare with the simulations of the X-ray structure (Figure ) and to investigate whether using experimental or designed structures affects the outcome of the free energy calculations. For each design, the sequence, register, topology and oligomerisation state were fixed, with the radius, interface angle and pitch allowed to vary. In the case of antiparallel assemblies, an additional parameter was included to modulate the offset between the helices. Designs were chosen based on their BUDE scores and the convergence of the design process. The chosen designs were also capped with acetyl and amide groups at the N-and C-termini of each helix respectively. Further details about the design process and parameters can be found in the SI (SI Section 2) and at michellab/CCmetaD.