Conformational profile of 1-aminocyclopropanecarboxylic acid

Abstract.

1-Aminocyclopropanecarboxylic acid (Ac₃c) is a constrained α amino acid residue that exhibits peculiar conformational characteristics. The aim of the present study is to provide a deeper understanding of these features to be used as guidance to decide when to choose Ac₃c as a building block for the design of peptide and protein surrogates. The whole Ramachandran plot of the Ace-Ac₃c-NCH₃ dipeptide was investigated at the Hartree–Fock level using a 6-31G(d) basis set and the most favorable structures were assessed on this surface by energy minimization. These results were subsequently used as a reference to generate specific molecular mechanics parameters for Ac₃c compatible with the parm94 set of the AMBER force field. The effect of water as a solvent on the conformational profile of the dipeptide was also assessed using the Miertus–Scrocco–Tomasi self-consistent reaction-field model at the Hartree–Fock level using a 6-31G(d) basis set and using the AM1 semiempirical method. The conformational profile of the Ac₃c dipeptide can be characterized by two symmetric low-energy regions for values of φ around ±80° with a wide range of values for ψ ranging from −40 to 180°, with the lower areas located at low values of ψ. Solvent effects do not alter the features of the conformational map, but a shift of the two absolute minima to (φ, ψ) values near (±90°, 0°) can be observed. These results are in accord with all experimental evidence and with the known tendency of Ac₃c to induce β-turn conformations in peptides.