Comparison of properties of Aib-rich peptides in crystal and solution: a molecular dynamics study

In order to study the differences of the structural properties of Aib-rich peptides in solution and in the crystalline state, molecular dynamics (MD) simulations of the Aib-containing peptide II (pBrBz-(Aib)5-Leu-(Aib)2-OMe) were performed in the crystalline state, starting from two different conformers obtained experimentally by X-ray diffraction. The structural properties as derived from X-ray crystallography (e.g., torsional angles and hydrogen bonds) are well-reproduced in both constant-volume and constant-pressure simulations, although the force-field parameters used result in a too-high density of the crystals. Through comparison with the results from previous MD and nuclear magnetic resonance (NMR) studies of the very similar peptide I (Z-(Aib)s-Leu-(Aib)2-OMe) in dimethylsulfoxide (DMSO) solution, it is found that, in the crystal simulation, the conformational distribution of peptide II is much narrower than that in the solution simulation of peptide. I. This leads to a significant difference in 3 [symbol: see text] (HN, HC alpha) coupling constant values, in agreement with experimental data, whereas the NOE intensities or proton-proton distance bounds appear insensitive to the difference in conformational distribution. For small peptides the differences between their conformational distribution in the crystalline form and in solution may be much larger than for proteins, a fact which should be kept in mind when interpreting molecular properties in the solution state by using X-ray crystallographic data.