Theoretical Comparison between Three-Point and Two-Point Binding Modes for Chiral Discrimination upon the N-Terminal Sequence of 3 sub(10)-Helix

• Published in: Polymer journal Vol. 38; no. 5; pp. 432 - 441
• Main Authors: Inai, Yoshihito, Ousaka, Naoki, Miwa, Yoichi
• Format: Journal Article
• Language: English
• Published: 01-05-2006
• Subjects: Amino acids; Binding energy; Categories; Density; Mathematical models; Optimization; Peptides; Segments
• ISSN: 0032-3896
• DOI: 10.1295/polymj.38.432

Complex structure and its energy were theoretically predicted between the N-terminal segment of right-handed 3 sub(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 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 3 sub(10)-helical N-terminus to discriminate the chirality of N-carbonyl-blocked peptide acid molecule.