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

Abstract

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.

The Odd Faces of Oligomers: The Case of TRAF2-C, A Trimeric C-Terminal Domain of TNF Receptor-Associated Factor

“…Aromatic residues are particularly abundant at interfaces, participating in both inter-chain and intra-chain interactions [ 38 ]. Thanks to their hydrophobic propensity, their rings can stabilize the subunits complex [ 39 ], being at the same time important for protein-protein recognition [ 40 ]. The analysis of TRAF2-C crystal structure demonstrates that two phenylalanines (F354 and F491) from one subunit and two tyrosines (Y350 and Y386) from another are located at interfaces.…”

Stackable Aromatic Dipeptide Ring Structures toward Nanotube Formation: Thermodynamics and Interactions in Gas‐Phase and Solution

“…[11][12][13] Building on these advancements, current studies are looking at other possible protein-like NTs that can be formed from modified FF, [14] l/d amino acids, [15][16][17] and dipeptides from the combination of other aromatic amino acids tryptophan (W) and tyrosine (Y). [18][19][20][21][22] The crystal structure of FFNTs has been well elucidated, [23][24][25][26][27] involving stacks of hexameric rings of FF in a head-to-tail conformation for intramolecular hydrogen bonding. [24,25,28] A single FFNT has an inner diameter of about 10 Å, while the bundles result in tubes with outer diameters ranging from 100-150 nm.…”

“…Previously, we studied the noncovalent interactions of tryptophan-and tyrosine-based dipeptide monomers and dimers. [18,19] In this paper, we present the results of extending the bottom-up approach beyond the dimeric size to investigate the stabilities and the underlying interaction energies of the dipeptide systems phenylalanine-tyrosine (FY), tryptophantyrosine (WY), and dityrosine (YY), in both their cyclic and linear forms. We provide insights into the thermodynamics of their formation into oligomeric ring structures of quadmeric, pentameric, hexameric, and heptameric sizes, both in the gas phase and in solution, by quantifying their formation energies.…”

“…FFNTs have also been explored for use in the biomedical field as biomimetic scaffolds, sensors, and drug delivery agents due to their relatively nontoxic properties [11–13] . Building on these advancements, current studies are looking at other possible protein‐like NTs that can be formed from modified FF, [14] l/d amino acids, [15–17] and dipeptides from the combination of other aromatic amino acids tryptophan (W) and tyrosine (Y) [18–22] …”

“…Previously, we studied the noncovalent interactions of tryptophan‐ and tyrosine‐based dipeptide monomers and dimers [18,19] . In this paper, we present the results of extending the bottom‐up approach beyond the dimeric size to investigate the stabilities and the underlying interaction energies of the dipeptide systems phenylalanine‐tyrosine (FY), tryptophan‐tyrosine (WY), and dityrosine (YY), in both their cyclic and linear forms.…”