Conformational space analysis of protected N-formyl-L-phenylalanine-N-amide amino acid: Effects of 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) have been explored using an efficient genetic algorithm combined with DFT and MP2 calculations in order to explore and investigate all potential minima on its potential energy surface (PES). The calculations carried out on this system have revealed that conformational building units corresponding to the right-handed helical (αL [φPhe = –60°, ψPhe = –60°]) and polyproline II (εL [φPhe = –60°, ψPhe = 180°]) are still missing from its PES and the inverse gamma turn (γL [φPhe = –60°, ψPhe = 60°]) form was the preferred for this compound in accordance with the ab initio and DFT calculation results. Furthermore, this study has shown that the sensitivity of the conformational preferences of the HCO—L—Phe—NH2 structures between B3LYP to MP2 optimizations are due to a significant contribution of the Basis Set Superposition Error (BSSE) effect and 6-311++G(2d,2p) basis set is more suitable for estimation of intramolecular interactions within this residue. Comparison between the theoretical calculations and the experimental data of X-ray crystallography extracted from protein data bank (PDB) shows promising similarities, which opens the way for possible future applications on large-molecular systems.