These results demonstrate that our protocol correctly predicts the preferred oligomerisation states of CC-Di, CC-Tri and CC-Tet. The differences between their ∆G • bind,total /helix and those of the alternative competing states suggest a complex free energy landscape, where a few mutations at the hydrophobic core can profoundly alter the preferred oligomerisation states. We then turned our attention to a pH-switchable system, CC-Hex*-L24E, which forms a parallel hexamer at pH 2-6.5 and an antiparallel tetramer with an offset at pH >7 (Figure ). The L24E mutation in the parent hexamer CC-Hex* introduces an acidic residue at one of the a positions at the hydrophobic core of the assembly. This is tolerated at low pH values, where the Glu residues are more likely to be protonated and can form a hydrogen bond network further stabilising the core. However, at higher pH values, the Glu residues are more likely to be deprotonated and negatively charged, and the subsequent repulsion in the otherwise hydrophobic core result in the destabilisation of the hexamer and a large structural re-arrangement, which leads to formation of the antiparallel tetramer. This is an inherently more challenging system, since the two structurally distinct states must be close in the free energy landscape to allow switching upon changes in the pH. The obtained ∆G • bind,total /helix values correlate with the experimentally observed states, namely the parallel hexamer is more favourable at low pH, and the antiparallel tetramer is more favourable at high pH (Figure , Tables ). Additionally, the ∆G • bind,total /helix value of the hexamer at low pH (-5.3 ± 1.3 kcal mol -1 , Table ) is consistent with that of the tetramer at high pH (-5.4 ± 1.1 kcal mol -1 , Table ), which is in agreement with the experimentally determined switching behaviour of the complex. As before, the cost of folding each helix has been implicitly accounted for by dividing the ∆G • bind,total with the number of helices in the complex. This folding cost will likely change as the pH changes; indeed, calculations of the percentage of helicity of the CC-Hex*-L24E monomer with Agadir show 13% helicity at pH 2 and 9% helicity at pH 8.5, with intermediate helicities in the pH range 2.5-8.5. This implies that there will be a higher cost of folding each monomer at low pH, potentially rendering the binding free energies at low pH less favourable. These monomer helicity calculations agree with experimental data which portray the CC-Hex*-L24E complex as highly helical at pH 3-5 and less helical at pH 6-7. However, this will likely not change the results significantly, as a small difference in monomer helicity is not expected to dramatically change the energetic cost of folding between the low and high pH conditions.