Structure, spectra and the effects of twisting of β-sheet peptides.: A density functional theory study

The structure, infrared (IR) absorption and vibrational circular dichroism (VCD) spectra and their response to twisting of a model peptide dimer (Ac-Ala(3)-NHMe)(2) in vacuum is calculated with density functional theory (DFT) methods at the BPW91/6-31G** level and compared in terms of twisting energetics to HF and MM level results. The differences in spectral frequencies and IR and VCD intensity distributions for fully relaxed parallel and anti-parallel beta-sheet arrangements, as well as for sheets with constrained twist are discussed and contrasted with known experimental data. Due to the hydrogen bonds between the strands, short (4 amide) strands assembled into beta-sheets were found to be stable in vacuum with DFT, unlike the case for helical conformations. For these optimized beta-structures, calculated IR spectra for parallel and anti-parallel alignments are distinguishable for the minimum energy structures and respond differently to twist distortion. The associated VCD intensity patterns reflect the sense of the sheet twists and are also predicted to discriminate between parallel and anti-parallel forms. (C) 2004 Elsevier B.V. All rights reserved.