title: Redox-Driven Conformational Dynamics in a Photosystem-II-Inspired β-Hairpin Maquette Determined through Spectroscopy and Simulation.
abstract: Tyrosine-based radical transfer plays an important role in photosynthesis, respiration, and DNA synthesis. Radical transfer can occur either by electron transfer (ET) or proton coupled electron transfer (PCET), depending on the pH. Reversible conformational changes in the surrounding protein matrix may control reactivity of radical intermediates. De novo designed Peptide A is a synthetic 18 amino-acid β-hairpin, which contains a single tyrosine (Y5) and carries out a kinetically significant PCET reaction between Y5 and a cross-strand histidine (H14). In Peptide A, amide II' (CN) changes are observed in the UV resonance Raman (UVRR) spectrum, associated with tyrosine ET and PCET; these bands were attributed previously to a reversible change in secondary structure. Here, we use molecular dynamics simulations to define this conformational change in Peptide A and its H14-to-cyclohexylalanine variant, Peptide C. Three different Y5 charge states, tyrosine (YH), tyrosinate (Y-), and neutral tyrosyl radical (Y·), are considered. The simulations show that Peptide A-YH and A-Y-retain secondary structure and noncovalent interactions, whereas A-Y· is unstable. In contrast, both Peptide C-Y-and Peptide C-Y· are unstable, due to the loss of the Y5-H14 π-π interaction. These simulations are consistent with previous UVRR experimental results on the two β-hairpins. Furthermore, they demonstrate the ability of simulations using fixed-charge force fields to accurately capture redox-linked conformational dynamics in a β-strand peptide.
authors.affiliation: School of Materials Science and Engineering, ‡School of Chemistry and Biochemistry, §Petit Institute for Bioengineering and Biosciences, and ∥School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Hyea
authors.initials: H
authors.lastname: Hwang
authors.affiliation: School of Materials Science and Engineering, ‡School of Chemistry and Biochemistry, §Petit Institute for Bioengineering and Biosciences, and ∥School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Tyler G
authors.initials: TG
authors.lastname: McCaslin
authors.affiliation: School of Materials Science and Engineering, ‡School of Chemistry and Biochemistry, §Petit Institute for Bioengineering and Biosciences, and ∥School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Anthony
authors.initials: A
authors.lastname: Hazel
authors.affiliation: School of Materials Science and Engineering, ‡School of Chemistry and Biochemistry, §Petit Institute for Bioengineering and Biosciences, and ∥School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Cynthia V
authors.initials: CV
authors.lastname: Pagba
authors.affiliation: School of Materials Science and Engineering, ‡School of Chemistry and Biochemistry, §Petit Institute for Bioengineering and Biosciences, and ∥School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Nevin
authors.affiliation: School of Materials Science and Engineering, ‡School of Chemistry and Biochemistry, §Petit Institute for Bioengineering and Biosciences, and ∥School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Pavlova
authors.affiliation: School of Materials Science and Engineering, ‡School of Chemistry and Biochemistry, §Petit Institute for Bioengineering and Biosciences, and ∥School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: Bridgette A
authors.identifier: 0000-0003-3421-1407
authors.initials: BA
authors.lastname: Barry
authors.affiliation: School of Materials Science and Engineering, ‡School of Chemistry and Biochemistry, §Petit Institute for Bioengineering and Biosciences, and ∥School of Physics, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
authors.forename: James C
authors.identifier: 0000-0002-1510-7842
authors.initials: JC
authors.lastname: Gumbart
mesh_terms: D004579:Electron Transport; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D045332:Photosystem II Protein Complex / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013057:Spectrum Analysis
chemical_list: D045332:Photosystem II Protein Complex