A first-principles investigation of histidine and its ionic counterparts

Abstract

Histidine (His) is an essential amino acid found to be a key residue in the active site and catalytic domain of many enzymes. Understanding the conformational preferences and the role of non-covalent interactions in the stability of this amino acid is of outstanding relevance in biological systems. The systematic study of the conformational space of His and its ionized counterparts in two tautomeric forms has been carried out using density functional theory. This study identified 33, 7, 9 and 11 distinct conformations on the potential energy surface (PES) of the His(N^τH) tautomer in its neutral, zwitterionic, anionic and cationic states, respectively. On the other hand, the PES of the His(N^πH) tautomer features 30, 12, 12 and 5 distinct conformers for the neutral, anionic, cationic and zwitterionic forms, respectively. Atoms-in-molecules analysis was employed to identify the nature of various non-covalent interactions such as hydrogen bonds, NH–π, OH–π and CH–O interactions. The conformers with NH–O hydrogen bonds are more stable than the conformers with other non-covalent interactions. In more general terms, the ability to form non-covalent interactions is a key determinant for conformational preferences of His and its ionic counter parts.