Table 1.

Core and electrostatic pairings for all 36 coiled-coil pairs.

All are grouped into desired pairs, intrapair off-target pairs and interpair off-targets pairs and ranked in order of T_m and according to core arrangement. Grey boxes show interactions including peptide 5 or 6 that may involve adoption of antiparallel conformations. Predicted energetic contributions to stability for heterospecific targets, homodimeric off-targets, heterodimeric off-targets (pairs) and heterodimeric off-targets (quadruples) are shown. Heterospecific pairs are predicted to have a ΔG_Core of − 23.2 kcal/mol based on free energy scored derived from a double mutant analysis [18], [19]. This is identical in homodimeric off-target pairs but is disfavoured for intrapair heterodimeric off-targets (ΔΔG = + 21.2 kcal/mol) and interpair heterodimeric off-targets (ΔΔG = + 10.6 kcal/mol). Similarly, heterospecific pairs are predicted to have a ΔG_{Electrostatic} of − 9.6 kcal/mol based on free energy scores [20]. This is strongly disfavoured in homodimeric off-target pairs (ΔΔG = + 7.2 to + 12.8 kcal/mol) and is disfavoured, although less so, for intrapair and interpair heterodimeric off-targets (ΔΔG = + 3.6 to + 6.4 kcal/mol). Inspection of these energies shows that (i) heterospecific pairs contain two II and two NN core pairings and fully complementary electrostatic e-g pairings, that (ii) homodimer instability is driven entirely by electrostatic repulsion, that (iii) off-targets within interactomes of peptide 1-4 or 5-8 are disfavoured driven mostly by the core residues (at a ratio of approximately 3–6:1) and that (iv) off-target interactions between peptides 1-4 and 5-8 are disfavoured driven mostly by the core residues (at a ratio of approximately 1.5–3:1). Sequence-specific E/K patterns are discussed with reference to normalised core configurations.

[Core free energy scores II = − 9.2 kcal/mol, NN = − 2.4 kcal/mol (Δ + 6.8) and NI = − 0.5 kcal/mol (Δ + 8.7)] [18], [19].

[Electrostatic free energy scores EK/KE = − 1.2 kcal/mol, EE = + 0.4 kcal/mol (Δ + 1.6) and KK = − 0.3 kcal/mol (Δ + 0.9)] [20].