The tertiary structure of the TC5b miniprotein is stabilized by inter-residue interactions of the Trp-cage, which is composed of a Tyr and several Pro residues surrounding a central Trp residue. The interactions include Ar-Ar (aromatic side-chain-aromatic side-chain), Ar-NH (aromatic side-chain-backbone amide), and CH-pi (aromatic side-chain-aliphatic hydrogen) interactions. In the present work, the strength of the weakly polar interactions found in the TC5b miniprotein was quantified using all of the available 38 NMR structures (1L2Y) from the Protein Data Bank with DFT quantum chemical calculations at the BHandHLYP/cc-pVTZ level of theory and molecular fragmentation with capping of the partial structures. The energies of interaction between the individual residues of the Trp-cage range between- 5.85 +/- 1.41 and -21.30 +/- 0.88 kcal mol(-1), leading to a significant total structural stabilization energy of -52.13 +/- 2.56 kcal mol(-1) of which about 50% is from the weakly polar interactions. Furthermore, the strengths of the individual weakly polar interactions are between -2.32 +/- 0.17 and -2.93 +/- 0.12 kcal mol(-1) for the CH-pi interactions, between -2.48 +/- 0.97 and -3.09 +/- 1.02 kcal mol(-1) for the Ar-NH interaction and -2.74 +/- 1.06 kcal mol(-1) for the Ar-Ar interaction.