Data Supplement

• Supplemental Data -

  Supplemental Table 1 - Hydrogen bonds with more than 40% of occurrence between ³²TRQRY³⁶-NH₂ (corresponding to PYY and truncated analogs peptides) and WT-hY₂
  

  Supplemental Table 2 - K_i values of PYY-(3-36) analogues for WT-hY₂ and its mutants. The K_i value of PYY-(3-36) for the WT-hY₂ (0.46 nM), as determined with SPA assay method, was used as a reference to calculate the fold changes of K_i values of other analogues and mutants, indicated in parenthesis
  

  Supplemental Table 3 - Additional mutations generated along this project, all of which revealed to have negligible effects on PYY-(3-36) binding
  

  Supplemental Table 4 - Free energies of binding (in kcal/mol) of PYY for the hY₂ mutants, calculated by FEP, and experimental values^a

  Supplemental Figure 1 - Sequence alignment of the NPY and PYY peptides

  Supplemental Figure 2 - Sequence and chemical formulae of PYY and analogues

  Supplemental Figure 3 - Analysis of the secondary structure in time for PYY peptide and shorter analogues in complex with Y₂

  Supplemental Figure 4 - Analysis of the secondary structure in time for PYY peptide and shorter analogues in water

  Supplemental Figure 5. Scatter plot of the calculated (Y axis) versus experimental (X axis) relative binding free energies (DDG, kcal/mol) for PYY-(3-36) to nine selected hY₂ mutants compared to WT-hY₂