Eur. Phys. J. D 20, 481-497 (2002)
https://doi.org/10.1140/epjd/e2002-00155-6

The role of enhanced aromatic π-electron donating aptitude of the tyrosyl sidechain with respect to that of phenylalanyl in intramolecular interactions

¹ Department of Biomedical Sciences, School of Medicine Creighton University, 2500 California Plaza, Omaha, NE 68178, USA
² Global Institute Of Computational Molecular and Material Science @ Velocet, 210 Dundas St. W., Toronto, Ontario, Canada M5G 2E8
³ Department of Chemistry, University of Toronto, Lash Miller Chemical Laboratories, 80 St. George St., Toronto, Ontario, Canada M5S 3H6

Corresponding authors: ^a gchass@fixy.org - ^b slovas@bif1.creighton.edu - ^c barrym@creighton.edu - ^d icsizmad@fixy.org

Received: 1 February 2002
Revised: 28 May 2002
Published online: 13 September 2002

Abstract

An exhaustive ab initio and DFT search for energetically stable conformers from the topologically possible set was undertaken on the N-acetyl-phenylalanyl-N-methylamide and N-acetyl-tyrosyl- systems. The geometries of all 81 phenylalanyl and 162 tyrosyl possible rotamers, described under the rules outlined by Multi-Dimensional Conformational Analysis (MDCA), were attempted at each of the RHF/3-21G, RHF/6-31G(d) and B3LYP/6-31G(d) levels of theory. A total of 32 and 66 stable conformational minima were found for the phenylalanyl and tyrosyl amino acid diamides, respectively, at the B3LYP/6-31G(d) level. From the tyrosyl set, 33 unique conformers emerge when the orientation of the dihedral angle (p-OH orientation) is disregarded. A total of 31 conformers were common to both sets and showed nearly identical geometries. The comparison of the optimized DFT geometries of the two systems showed near by perfect linear fits with R² values of 0.9997, 0.9994, 0.9997, and 0.9996 for the , , , and dihedral angles, respectively. Relative energies of the matching 31 conformers also fitted to a linear plot with an R² value of 0.9985. The geometric centroid of the aromatic ring in the sidechain of both systems was found to be within 4.1 Å of the H and O atoms of the peptide groups, in 21 and 2 of the conformers, respectively. None of the non-matching conformers showed any such interaction distance ≤4.1 Å.