title: Conformational properties of the Pro-Gly motif in the D-Ala-l-Pro-Gly-D-Ala model peptide explored by a statistical analysis of the NMR, Raman, and Raman optical activity spectra.
abstract: The Pro-Gly sequence in designed peptides and proteins is often used to mimic natural beta-hairpin turns. Shorter peptides containing this moiety, however, adopt multiple conformations, and their propensity to form the turn is not obvious. In this study, conformational flexibility of Pro-Gly was investigated with the aid of NMR, Raman scattering, and Raman optical activity (ROA). The spectra of a model tetrapeptide NH3+-D-Ala-L-Pro-Gly-D-Ala-CO2- were analyzed on the basis of statistical methods and density functional computations. Other peptide derivatives were adopted as supporting theoretical and experimental models. The results suggest that the loop conformation of the Pro-Gly core is not inherently stable in vacuum. On the other hand, in aqueous environment the propensity to form the beta-hairpin loops is an intrinsic property of the Pro-Gly sequence. It was observed also in a shorter Ac-D-Pro-Gly-NH-Me dipeptide. The attached alanine residues in the tetrapeptide stabilize the structure only partially. Thus an inclusion of the solvent in the calculations is important for correct description of peptide folding in the aqueous environment. The agreement of the optical spectra with the experiment was determined from overlaps between simulated and measured spectral curves. The comparison of the computed NMR, Raman, and ROA was hampered by experimental noise and limited accuracy of the computations. However, the statistical analysis of the spectroscopic data provided conformer distribution consistent with the computation of the relative energies. The combination of the NMR and Raman techniques with the quantum computations appeared very beneficial for the investigation of Pro-Gly conformational behavior, and can be recommended for future peptide folding studies.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo nAm. 2, 16610, Prague 6, Czech Republic.
authors.forename: Milos
authors.initials: M
authors.lastname: Budesínský
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Sebestík
authors.forename: Lucie
authors.initials: L
authors.lastname: Bednarova
authors.forename: Vladimír
authors.initials: V
authors.lastname: Baumruk
authors.forename: Martin
authors.initials: M
authors.lastname: Safarík
authors.forename: Petr
authors.initials: P
authors.lastname: Bour
mesh_terms: D020816:Amino Acid Motifs; D002152:Calorimetry, Differential Scanning; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013059:Spectrum Analysis, Raman / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D009842:Oligopeptides