Theoretical comparison between three-point and two-point binding modes for chiral discrimination upon the N-terminal sequence of 310-helix

Complex structure and its energy were theoretically predicted between the N-terminal segment of right-handed 310 -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 [straight phi] 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 310 -helical N-terminus to discriminate the chirality of N-carbonyl-blocked peptide acid molecule.