The spatial organization of the human hemokinin-1 and mouse/rat hemokinin-1 molecules

Abstract

The conformational characteristics of human hemokinin-1 and mouse/rat hemokinin-1, two molecules of the tachykinin family, each of which consists of 11 amino-acid residues, were investigated using the molecular-mechanics method. Using the step-by-step approach, we determined the energetically favorable spatial structures of these molecules and their fragments, which were represented as sets of conformations that are characterized by a relatively labile N-terminal tripeptide and a conformationally rigid C-terminal segment. It was shown that the conformationally conservative C-terminal octapeptides of these molecules preferably acquire two conformations with different structures of the peptide chain: one of them is an α-helical structure and the other contains a chain turn followed by an α-helical turn at the C-terminal end. The calculations determined the favorable ranges for the values of the dihedral angles and orientations of all residues in low-energy conformations of hemokinin molecules. An analysis of the conformations of individual fragments made it possible to reconstruct the formation of the secondary structures in these molecules. These results were used to determine the energy contributions of interactions among the residues and to evaluate the role of each residue in the formation of the optimal spatial structures of hemokinin-1 molecules.