Ultrafast spectroscopy reveals subnanosecond peptide conformational dynamics and validates molecular dynamics simulation

Abstract

Femtosecond time-resolved spectroscopy on model peptides with built-in light switches combined with computer simulation of light-triggered motions offers an attractive integrated approach toward the understanding of peptide conformational dynamics. It was applied to monitor the light-induced relaxation dynamics occurring on subnanosecond time scales in a peptide that was backbone-cyclized with an azobenzene derivative as optical switch and spectroscopic probe. The femtosecond spectra permit the clear distinguishing and characterization of the subpicosecond photoisomerization of the chromophore, the subsequent dissipation of vibrational energy, and the subnanosecond conformational relaxation of the peptide. The photochemical cis͞trans-isomerization of the chromophore and the resulting peptide relaxations have been simulated with molecular dynamics calculations. The calculated reaction kinetics, as monitored by the energy content of the peptide, were found to match the spectroscopic data. Thus we verify that all-atom molecular dynamics simulations can quantitatively describe the subnanosecond conformational dynamics of peptides, strengthening confidence in corresponding predictions for longer time scales.

Molecular dynamics simulation exploration of unfolding and refolding of a ten-amino acid miniprotein

“…Moroder et al have synthesized various peptides, in which an azobenzene unit was incorporated directly in the backbone (Renner et al 2000a, b;Cattani-Scholz et al 2002). An optical laser pulse excites the molecular system and then azobenzene will perform cis-trans photoisomerization, which cause subsequent conformational dynamics of the peptide backbone (Nguyen and Stock 2006;Smith 2007, 2008;Spörlein et al 2002).…”

Synthesis of 3,3′-bis(sulfonato)-4,4′-bis(chloroacetamido)azobenzene and cysteine cross-linking for photo-control of protein conformation and activity

“…Intermolecular cross-linking between proteins was not apparent in any of these cases and was likely suppressed by the fast intramolecular reaction between the chloroacetamide moiety of BSBCA and the second Cys residue. Photo-isomerization takes place rapidly, with high quantum yield, and occurs at wavelengths higher than 300 nm, so the light used to produce isomerization is not strongly absorbed by protein and nucleic acid present in biological targets 7,[24][25][26] .…”

Femtosecond fluorescence up-conversion spectroscopy of a rotation-restricted azobenzene after excitation to the S1state

“…[3][4][5][6][7][8] However, the detailed mechanisms and dynamics of this prototypical reaction are still a matter of controversy. A longstanding question is whether the isomerization takes place as ''inversion'' on one of the N atoms or as large-amplitude ''rotation'' about the central NN bond or whether it requires more complex nuclear motions.…”