Fig. 6. Effects of branching on staple behavior; (a) crystal structure of hydrocarbon cross-linked macrocyclic peptide (red, hydrocarbon staple: orange, PDB: 4N7Y) in complex with 14–3–3 (blue): computational analysis of the 14–3–3 surface reveals cavities 1 and 2 (green) in proximity to amino acids X(Me)_R3 and X(Me)_S6 that may be suitable sites through which to optimize affinity; (b) crystal structures of ESp (purple) and β_RS8 (PDB: 4N7G, red) bound to 14–3–3 (PDB: 4N7Y); (c) crystal structures of ESp (purple, PDB: 4N7G) and β_SS12 (red) in bound to 14–3–3 (PDB: 4N84);²⁸ (d) structure of branched stapling amino acids S₅, λ_S and λ_R; (e) SRC2-SP1 (salmon, PDB: 5DXB), SRC2-SP2 (orange, PDB: 5HYR), and SRC2-SP3 (purple, PDB: 5DX3) adopt conformations to alleviate syn-pentane interactions between the α- and γ-methyl groups.⁷⁴.