*2.5. Energy Partitioning*

The main workhorse for the energy partitioning in this work is the Functional-group SAPT (F-SAPT) method [46,47] and its intramolecular variant I-SAPT [105], which have been utilized to determine the inter- and intramolecular interactions between interesting groups of atoms. For this purpose, the partitioning on the SAPT0 level in the jun-cc-pVDZ basis set [93] was utilized. In the F-SAPT, both SAPT partitioning of the interaction energy into physically-sound components and the partitioning of these components into contributions, which can be attributed to the interactions between groups of atoms, are utilized, which gives us the opportunity to classify inter-group interactions not only in terms of their strength (i.e., by comparing the absolute value of the interaction energy) but also according to their dominant SAPT contribution. In practice, one usually examines electrostatics, first-order exchange, and effective induction and dispersion, which are obtained by adding up second-order induction, exchange-induction, and the *δ*EHF term, or second-order dispersion and exchange-dispersion, respectively. In order to facilitate the analysis, we developed a graph system [106], where groups of the molecule A and B are placed on the left and right edges of the graph and are connected with red (attractive) or blue (repulsive) lines, whose thickness is proportional to the absolute value of the component under study. It should be emphasized that both F- and I-SAPT energy partitionings should be treated with caution since such partitionings depend to some extent on the applied fragmentation approach. In the (F/I)-SAPT case, this fragmentation is orbital-based and therefore is dependent on the balanced description of various atoms and bonds within a given basis. It also contains contributions from the so-called "linkers", which appear at places where the bonds between groups are broken. The latter contributions are somewhat arbitrarily divided between adjacent groups in the reduced analysis; therefore, the analysis of tiny energy fluctuations for partitioned energies is of limited value. Numerous studies performed with either F-, or I-SAPT show [107–111] that many useful conclusions can be reached if one adheres to hints given in the original papers of Parrish et al.. Therefore, in this study, we apply a standard (for F-SAPT) jun-cc-pVDZ basis and the simplest SAPT0 rung of SAPT models, as advised in Ref. [46].

For purposes of the energy partitioning with F-SAPT, the selected functional groups for the case of calixarenes are: hydroxy (OH), phenyl (Ph), methylene (CH2), and *tert*butyl groups (in order to make an easier comparison of the calix[6]arene and hexa-*p*-*tert*butylcalix[6]arene we separated the *para* hydrogen atom in the phenyl ring as a separate group–this hydrogen is replaced by the *tert*-butyl group in the latter molecule). The common functional groups of amino acids are: amino (NH2) and carboxy (COOH) groups.

Depending on the amino acid type, other functional groups are singled out (see F-SAPT graphs for all the complexes under study in the Supplementary Information). For instance, for the simplest Gly, the only remaining group is the methylene group CH2, while for the Phe amino acid, there are additionally the ring and CH groups. We have chosen not to fragment the carboxy group into C=O and OH; therefore, in some cases, the possible classification of the bonding involving this group as the H-bond (or not) will require a visual check.

For sake of conciseness, we define a calixarene "unit" consisting of a phenolic group (i.e., either a phenol group or *tert*-butyl-substituted phenol group) and a methylene bridge, and we will number these units as in Figure 2. If necessary, the respective groups within these units will be distinguished by adding a number behind the group (i.e., OH-*k*, Ph*k*, CH2-*k*, *tert*-butyl-*k* denote the hydroxy, phenyl, methylene, and *tert*-butyl groups of the *k*th calixarene unit, respectively). Analogously, we will differentiate the group X of an amino acid Y as X-Y, e.g., the COOH group of Gly will be denoted as COOH-Gly to avoid confusion.

**Figure 2.** A numeration of calixarene groups for *pc*, *al*, and *wc* conformers (upper, middle, and lower rows, correspondingly). Colors correspond to the following numbers: orange–1, yellow–2, green–3, cyan –4, blue –5, violet– 6.

For the case of the SMF, the molecular units are selected automatically and grouped into fragments by the fragmentation procedure; therefore, in several cases, two or more interesting groups are placed together in one fragment. Nevertheless, by a difference analysis, one can often determine the main "culprit" for a strong interaction within the fragments. These analyses of SSMF3 pair interaction energies between fragments of molecules A and B give us a complementary view of the interaction energy partitioning.

The F-SAPT and I-SAPT partitionings, SAPT0 and most MP2 and SCS-MP2 calculations have been performed with the Psi4 program [112]. Some supermolecular calculations were performed with Molpro [103].
