Structure of N-acetylproline amide in liquid water: Experimentally measured and numerically simulated infrared and vibrational circular dichroism spectra

A few experimental and theoretical studies on the molecular structure of N-acetylproline amide (AP) in D₂O solution have been reported recently. However, there is no consensus of the precise structure of AP in D₂O because spectroscopically determined structures and a theoretically simulated one have been found to be different from one another. To determine its aqueous solution structure, IR and vibrational circular dichroism spectra of both L- and D-form AP solutions were measured. Molecular dynamics simulations with two different force fields and density functional theory calculations for the trans and cis rotamers of AP were performed to numerically simulate those spectra. Comparisons between experimentally measured and computationally simulated spectra directly suggest that the AP in water adopts a polyproline II-like conformation and that the force field parameter ff03 in the AMBER 8 suite of programs is more realistic and reliable in predicting molecular structure of AP in water than the ff99 in AMBER 7.