Peptides as Model Systems for the Unfolded State of Proteins Explored By Vibrational Spectroscopy

Abstract

Unfolded proteins are generally thought to be structurally random with a minimum of non‐local interactions. This concept implies that with the exception of glycine and proline the conformational propensities of amino acid residues in polypeptides should be comparable in that they all sample the statistically allowed region of the Ramachandran plot. However, over the last ten years experimental and computational evidence has emerged for the notion that the conformational space of residues might be more restricted than predicted by random or statistical coil models. We have developed several algorithms which can be used to simulate the amide I band profile of the IR, isotropic Raman, anisotropic Raman and Vibrational Circular Dichroism (VCD) spectra of polypeptides based on assumed ensembles of side chain conformations. The simulations are generally restricted by 3JcαHNH coupling constants obtained from NMR spectroscopy. A comparison with experimental results reveals that e.g. alanine has a clear preference...