*2.4. Helical Propensities Show Different Binding Patterns*

The binding ensembles produce a higher helical content with respect to the freepeptide simulations. Figure A8 shows the three anchoring residues to be predominantly in helical conformations for *pdiq* and *ATSP*-7041. *p53* is well known to make a helix in the N-terminal region of the peptide which our simulations reproduce. The *Ala1* control sequence, which has three anchoring residues, is also able to adopt helical conformations, to a lesser extent. The spacing of the anchoring residues in the sequence (residues *i*, *i* + 4 and *i* + 7) and the size of the binding site favor helical conformations for the simultaneous interaction inside the active site. However, the *Ala2* control, adopts very small amounts of helical conformations for two of the three anchoring regions, consistent with the lack of anchoring residues to stabilize those conformations. Not surprisingly, the peptides with larger helical content also have narrower conformational ensembles at low replica index (*ATSP*-7041 and *pdiq*), whereas *p53*, *Ala1*, and *Ala2* have progressively larger ensembles at the lowest temperature replica.
