A Molecular Dynamics Study of the Stereoselective Interaction between an Enantiomeric Amino-Acid Ester and an l-Histidine-Containing Catalyst in the Bilayer Membrane

Abstract

Molecular dynamics simulations were performed to investigate the stereoselective interaction between an enantiomeric amino acid substrate (N-acylated-l-phenylalanine-p-nitrophenyl ester) and an l-histidine-containing dipeptide catalyst (Nα-(N-benzyloxycarbonyl-l-leucyl)-l-histidine) in the bilayer of cationic surfactants (N,N-bisdodecyl-N,N-dimethylammonium chloride). We found that a catalyst–substrate complex, which had an interamide hydrogen bond, was formed spontaneously in vacuum at 500 K. This complex was found to be stable both in vacuum and in the bilayer membrane for 100 ps at 300 K. The distances between the hydrophobic side chains in the complex were consistent with experimental results. The interamide hydrogen bond was retained in the hydrophobic core of the membrane. These results suggest that the catalyst–substrate complex found in this work is relevant to the stereoselective hydrolysis of the l-enantiomer of the substrate.