Differentiation of beta-sheet-forming structures: Ab initio-based simulations of IR absorption and vibrational CD for model peptide and protein beta-sheets

Ab initio quantum mechanical computations of force fields (FF) and atomic p olar and axial tensors (APT and AAT) were carried out for triamide strands Ac-A-A-NH-CH3 clustered into single-, double-, and triple- strand beta -she et-like conformations. Models with phi, psi, and omega angles constrained t o values appropriate for planar antiparallel and parallel as well as coiled antiparallel (two-stranded) and twisted antiparallel and parallel sheets w ere computed. The FF, APT, and AAT values were transferred to corresponding larger oligopeptide beta -sheet structures of up o five strands of eight r esidues each, and their respective IR and vibrational circular dichroism (V CD) spectra were simulated. The antiparallel planar models in a multiple-st randed assembly give a unique IR amide I spectrum with a high-intensity, lo w-frequency component, but they have very weak negative amide I VCD, both r eflecting experimental patterns seen in aggregated structures. Parallel and twisted beta -sheet structures do not develop a highly split amide I, thei r IR spectra all being similar. A twist in the antiparallel beta -sheet str ucture leads to a significant increase in VCD intensity, while the parallel structure was not as dramatically affected by the twist. The overall predi cted VCD intensity is quite weak but predominantly negative (amide 1) for a ll conformations. This intrinsically weak VCD can explain the high variatio n seen experimentally in beta -forming peptides and proteins. An even large r variation was predicted in the amide II VCD, which had added complication s due to non-hydrogen-bonded residues on the edges of the model sheets.