Theoretical Comparison between Three-Point and Two-Point Binding Modes for Chiral Discrimination upon the N-Terminal Sequence of 310-Helix: Review Article

Complex structure and its energy were theoretically predicted between the N-terminal segment of right-handed 3 10 -helical peptide ( 1 ) and chiral acid based on various amino acids. Two categories of the chiral acids have been chosen. One is N -carbonyl-blocked amino acid for the three-point coordination to the N-terminal sequence of peptide 1 . The other acid for the two-point coordination contains no extra carbonyl groups. Energy minimization from the corresponding initial models was performed by semiempirical molecular orbital calculation. In each amino acid species, the three-point coordination, compared with the two-point type, tends to generate larger difference in energies of D -/ L -complexes, which are more stable for L -species bound to right-handed helix. In the three-point binding, N -carbonyl-blocked L -amino acid is prone to adopt negative φ values. Density functional method was also applied to smaller analogs, providing similar tendency in complex structure and energy difference. The predictions obtained here are fully consistent with our previous findings [Y. Inai et al. , J. Am. Chem. Soc. , 125 , 8151–8162 (2003)], in which preferential induction of right-handed helix in peptide 1 occurs with N -carbonyl-protected L -amino acid, but inefficiently with simple carboxylic acid. The energetic advantage for the three-point binding implies the function of 3 10 -helical N-terminus to discriminate the chirality of N -carbonyl-blocked peptide acid molecule.