Convex Constraint Decomposition of Circular Dichroism Curves of Proteins

A new algorithm, called convex analysis, has been developed to deduce the chiral contribution of the common secondary structures directly from experimental circular dichroism (CD) curves of a large number of proteins. The analysis is based on CD data reported by Yang et aU Test runs were performed on sets of artificial protein spectra created by the Monte Carlo technique using poly-u-Iysine based component spectra. Application of the decomposition algorithm for the created sets of spectra resulted in component spectra [B (2, i)] and weights [C (i, k)] with excellent Pearson correlation coefficients (r).2 The algori thm, independent of X-ray data, revealed that the CD spectrum of a given protein is composed of at least four independent sources of chirality. Three of the computed component curves show remarkable resemblance to the CD spectra of known protein secondary structures. This approach yields a significant improvement compared to the eigenvector analysis of Hennessey and Johnson." The new method is a useful tool not only in analyzing CD spectra but also in treating other decomposition problems where an additivity constraint is valid

Analysis of hydrogen bonds in peptides, based on the hydration affinity of amides

The difference in the affinity for water of peptide groups embedded in different molecular environments was investigated. The chemical shift of an amide proton is sensitive to conformational variations, as well as to changes in the molecular environment [D.S. Wishat, B.D. Sykes and F.M. Richards, J. Mol. Biol., 222 (1991) 311\u2013333]. Therefore, if the conformational motions are minimized or excluded, the observed changes in the chemical shift can simply be related to the environmental effects. The conformation(s) of the cyclic \u3b2-turn models studied in this work has been previously reported using X-ray, NMR, circular dichroism, and (FT-IR) spectroscopic methods, as well as MD calculations. [M. Holl\uf3si, K.E. K\uf6ver, S. Holly, L. Radics and G.D. Fasman, Biopolymers, 26 (1987) 1527\u20131572; A. Perczel, M. Holl\uf3si, B.M. Foxman and G.D. Fasman, J. Am. Chem. Soc., 113 (1991) 9772\u20139784; and H.H. Mantsch, A. Perczel, M. Holl\uf3si and G.D. Fasman, Biopolymers, 33 (1993) 201\u2013207]. The backbone of the cyclo[(\u3b4)Ava\u2014Gly\u2014Pro\u2014Aaa\u2014Gly] (where Aaa = Ser(OtBu), Ser or Thr(OtBu), and \u3b4(Ava) is \u3b4-aminovaleric acid) compounds was found to be rigidly incorporated in the structure and to contain two intramolecular hydrogen bonds. These \u3b2-turn models also include one (or two) \u201cfree\u201d amide group(s) that are not involved in any type of interaction. The \u201cwater titration\u201d of these amide groups in acetonitrile, where they are involved in various degrees of hydrogen bonding, revealed their molecular environment. Owing to the rigidity of these structures, the observed changes in the amide proton chemical shifts, during titration were attributed to their involvement in hydrogen bonding. This was confirmed by monitoring the water titration simultaneously with FT-IR spectroscopy. The phenomenon described here, with the proposed characterization of the investigated peptide/water system, comprise an improvement in the NMR method for analyzing the hydrogen bonding of small rigid peptides.Peer reviewed: YesNRC publication: Ye