Structural trends of tryptophan dimer: hydrogen bonding versus π-stacking from an energy decomposition analysis...

Identifying the energetic and structural properties of amino acid monomers that drive dimer formation can provide key insights into the non-covalent interactions responsible for their association. In this work, density functional theory, energy decomposition analysis (EDA), and conformer sampling are employed to analyze the interactions responsible for the dimerization of the zwitterionic amino acid tryptophan in implicit solvent. Although EDA suggests that charge transfer is the dominant stabilizing interaction, other distinct structure-energy relationships emerge. For instance, end-on and T-shaped conformations are primarily stabilized by charge transfer, contributing more than 1 kcal mol^-1 compared to dispersion in some cases. Alternatively, some π-stacked conformations are preferentially stabilized through dispersion by as much as 4 kcal mol^-1. To further analyze stabilization effects from hydrogen bonding (e.g., the effects of donor-acceptor orbitals during charge transfer), a complementary occupied-virtual pair analysis reveals that stacked conformers have relatively weaker donor-acceptor contributions to charge transfer compared to their end-on counterparts. Additionally, implicit solvation is found to destabilize binding for stacked conformations more strongly than for end-on structures. The analysis presented here provides insights into the role of the non-covalent interactions that enable amino acid dimerization elucidating the fundamental interactions responsible for self-aggregation.