Aromatic side‐chain contributions to the far ultraviolet circular dichroism of peptides and proteins

Abstract

Abstract The rotational strength of the L a transition in phenylalanine and tyrosine side chains has been calculated for dipeptides with various backbone and side‐chain conformations. Similar calculations have also been performed for tripeptides in the β‐turn conformation with aromatic residues at the corners of the turn. The interaction of the aromatic ring with neighboring peptides generates rotational strengths in the L a transition of the order of 0.1 Debye‐Bohr magneton. When the preferred backbone and side‐chain conformations are considered, it is found that the most probable conformations have positive L a bonds. This result accounts for the observation that the N ‐acyl amino acid amides of L ‐Tyr and L Phe have positive L a bands. It also suggests that, although other interactions may affect the numerical value and even the sign, there will be a significant positive contribution to the rotational strength of aromatic residues in globular proteins from nearest‐neighbor interactions. Calculations on proteins of known conformation at the nearest‐neighbor level confirm the tendency toward positive L a contributions for Phe and Tyr residues. This contribution can be of the order of 10% of the observed CD even in proteins with rather strong amide contributions. In some proteins, such as the gene 5 protein from bacteriophage fd and many snake‐venom toxins, side‐chain contributions from Tyr and Trp residues manifest themselves as positive CD bands in the 225–250‐nm region. The magnitude of the nearest‐neighbor contributions and the trend toward positive contributions are consistent with the observation of such CD bands in globular proteins. No special stacking interaction among aromatic side chains needs to be invoked.