Figure 18.6.3.1 Design of src SH3 binding to a target peptide

The energies are raw E_total values taken from the appropriate pdb files in examples/multistate/SH3_peptide/, and are not scaled by OVERALL_ENERGY_SCALE. The target affinity (E_bound - E_free) energies are shown in bold, while the specificity (affinity to target EALPPERPRY peptide with respect to competitor RALPPLPRY peptide) energies are shown in bold italics.

The multistate-optimized sequence includes several basic residues near the target peptide glutamates, and has a higher (worse) absolute energy for the bound state than the target-state optimized sequence. However, as discussed for coiled-coils (O'Shea et al 1992; Hendsch et al 1994), these groups preferentially destabilize the competitor states (unbound and non-target RALPPLPRY peptide bound), rather than stabilize the target state directly. This results in tighter affinity, as well as higher specificity for the target peptide. Unlike absolute energies, affinity and specificity are the experimentally and biologically relevant values.