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

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 Δ G 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.