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Conformational manifold of alpha-aminoisobutyric acid (Aib) containing alanine-based tripeptides in aqueous solution explored by vibrational spectroscopy, electronic circular dichroism spectroscopy, and molecular dynamics simulations
Journal article

Conformational manifold of alpha-aminoisobutyric acid (Aib) containing alanine-based tripeptides in aqueous solution explored by vibrational spectroscopy, electronic circular dichroism spectroscopy, and molecular dynamics simulations

Reinhard Schweitzer-Stenner, Widalys Gonzales, Gregory T Bourne, Jianwen A Feng and Garland R Marshall
Journal of the American Chemical Society, v 129(43), pp 13095-13109
31 Oct 2007
PMID: 17918837

Abstract

Amino Acid Sequence Temperature Vibration Molecular Conformation Models, Molecular Alanine - chemistry Oligopeptides - metabolism Protein Folding Aminoisobutyric Acids - chemistry Spectrophotometry, Infrared Solutions Computer Simulation Amides - chemistry Spectrum Analysis, Raman Circular Dichroism Oligopeptides - chemistry
Replacement of the alpha-proton of an alanine residue to generate alpha-aminoisobutyric acid (Aib) in alanine-based oligopeptides favors the formation of a 3(10) helix when the length of the oligopeptide is about four to six residues. This research was aimed at experimentally identifying the structural impact of an individual Aib residue in an alanine context of short peptides in water and Aib's influence on the conformation of nearest-neighbor residues. The amide I band profile of the IR, isotropic and anisotropic Raman, and vibrational circular dichroism (VCD) spectra of Ac-Ala-Ala-Aib-OMe, Ac-Ala-Aib-Ala-OMe, and Ac-Aib-Ala-Ala-OMe were measured and analyzed in terms of different structural models by utilizing an algorithm that exploits the excitonic coupling between amide I' modes. The conformational search was guided by the respective 1H NMR and electronic circular dichroism spectra of the respective peptides, which were also recorded. From these analyses, all peptides adopted multiple conformations. Aib predominantly sampled the right-handed and left-handed 3(10)-helix region and to a minor extent the bridge region between the polyproline (PPII) and the helical regions of the Ramachandran plot. Generally, alanine showed the anticipated PPII propensity, but its conformational equilibrium was shifted towards helical conformations in Ac-Aib-Ala-Ala-OMe, indicating that Aib can induce helical conformations of neighboring residues positioned towards the C-terminal direction of the peptide. An energy landscape exploration by molecular dynamics simulations corroborated the results of the spectroscopic studies. They also revealed the dynamics and pathways of potential conformational transitions of the corresponding Aib residues.

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Collaboration types
Domestic collaboration
Web of Science research areas
Chemistry, Multidisciplinary
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