Peptide structure determination by two-dimensional infrared spectroscopy in the presence of homogeneous and inhomogeneous broadening

Abstract

The potential information content of two-dimensional infrared (2D-IR) spectroscopy of the amide-I band as a structure analysis method of small peptides is explored in a computational study, applying it to a cyclic penta peptide as an example. In the presence of realistic homogeneous and inhomogeneous broadening, the structure resolution power in the case of a nonisotope labeled molecule would be vanishingly small. However, 2D-IR spectroscopy can reveal the structure of the peptide uniquely if using a sufficiently large set of isotope labeled compounds. Design strategies for isotope labeling are developed. In the case of the cyclic penta peptide studied here, at least three single C13 labeled compounds would be needed to determine the structure. While double C13 labeling does not offer any advantage compared to single C13 labeling, mixed C13O16–C12O18 or C13O16–C13O18 double labeling does. It is furthermore explored to what extent a structure can still be determined even under nonideal conditions, i.e., if systematic errors in the molecular models are allowed or if the molecule is allowed to coexists in different conformations simultaneously.