Binding properties of cucurbit[7]uril to neutral and protonated amino acids: A theoretical study

We systematically investigate the binding nature of cucurbit[7] (CB[7]) toward 20 amino acids in both neutral (AAs) and protonated (AAs⁺) states using quantum chemistry methods. The result indicates that, among AAs, Arg and Asn show the largest binding strength to CB[7], and for AAs⁺, Gln⁺ and Asn⁺ bind to CB[7] the strongest. The binding strength of protonated CB[7]/AA⁺ is much stronger than that of neutral CB[7]/AA counterpart due to the introduction of ion-dipole interaction and the increase in number and strength of hydrogen bonds. Energy decomposition analysis indicates that electrostatic interactions play major roles in both CB[7]/AAs and CB[7]/AAs⁺ complexes. Moreover, we analyzed the dependence of binding strength on single AA volume and dipole moment. This study is beneficial for providing valuable information in predicting the recognition sites for a sequence-based peptide or protein by CB[7] and rationally designing a synthetic host molecule for specific peptide or protein recognition.