To further validate CPCM's selective stabilization of MOs based on their local electrostatic environments, we extended our analysis to more MOs in the zwitterionic 3ftr. We focused on core orbitals that were minimally impacted by orbital relaxation at different ε values and, hence, are expected to follow the trend of Eqs. ( ) and ( ). To further simplify the comparison, we limited our analysis to MOs with very similar shapes but distinct local electrostatic environments. Based on these criteria, we selected the MOs corresponding to the 1s orbitals of the backbone atoms (N, Cα, C, O, N) of each residue, whose similarities and insensitivity to ε change were verified (Supplementary Material Text S2). Clear trends showed up as we plotted the orbital energy contribution by CPCM, 𝛥𝜖 ; %&%' , ordered by the spatial location of these orbitals (Figure ). The orbital energy change, 𝛥𝜖 ; %&%' , gradually transits from negative (stabilization) to positive (destabilization) as the location of the 1s orbital changes from the C-terminal (GLY-6) to the Nterminal (SER-1), meeting the expectation of Eq. ( ) and Eq. ( ). The same trend was observed for another three small zwitterionic peptides, 2ol9, 2onw, and 3fva (Supplementary Material Figure ).