Conformational Space Analysis of Protected N-Formyl-L-Phenylalanine-N-Amide Amino Acid: Effects of the Intramolecular Basis Set Superposition Error

Abstract

In the present work, the conformational space landscape of L-phenylalanine amino acid with protected N- and C-termini (HCO–L–Phe–NH₂) is explored using an efficient genetic algorithm combined with DFT and MP2 calculations in order to investigate all potential minima on its potential energy surface (PES). The calculations carried out on this system reveal that conformational building units corresponding to the right-handed helix (α_L [φ_Phe = −60°, ψ_Phe = −60°]) and polyproline II (ε_L [φ_Phe = −60°, ψ_Phe = 180°]) are still missing from its PES and the inverse gamma turn (γ_L [φ_Phe = −60°, ψ_Phe = 60°]) form is preferred for this compound in accordance with the ab initio and DFT calculation results. Furthermore, this study shows that the sensitivity of the conformational preference of HCO–L–Phe–NH₂ structures from B3LYP to MP2 optimizations is due to a significant contribution of the basis set superposition error (BSSE) effect and the 6-311++G(2d,2p) basis set is more suitable for the estimation of intramolecular interactions within this residue. The comparison between the theoretical calculations and the experimental X-ray crystallographic data extracted from the protein data bank (PDB) shows promising similarities, which opens the way for possible future applications on large molecular systems.