Probing the Nature of Noncovalent Interactions in Dimers of Linear Tyrosine-Based Dipeptides

[Image: see text] Tyrosine-based dipeptides self-assemble to form higher order structures. To gain insights into the nature of intermolecular interactions contributing to the early stages of the self-assembly of aromatic dipeptides, we study the dimers of linear dityrosine (YY) and tryptophan–tyrosine (WY) using quantum-chemical methods with dispersion corrections and universal solvation model based on density in combination with energy decomposition and natural bond orbital (NBO) analyses. We find that hydrogen bonding is a dominant stabilizing force. The lowest energy structure for the linear YY dimer is characterized by O(carboxyl)···H(O)(tyr). In contrast, the lowest energy dimer of linear WY is stabilized by O(carboxyl)···H(N)(trp) and π(tyr)···π(tyr). The solvent plays a critical role as it can change the strength and nature of interactions. The lowest energy for linear WY dimer in acetone is stabilized by O(carboxyl)···H(O)(tyr), π(trp)···H(C), and π(trp)···H(N). The ΔG of dimerization and stabilization energies of solvated dipeptides reveal that the dipeptide systems are more stable in the solvent phase than in gas phase. NBO confirms increased magnitudes for donor–acceptor interaction for the solvated dipeptides.