Theoretical and Computational Chemistry

Protein control of photochemistry and transient intermediates in phytochromes

Authors

  • Giacomo Salvadori Dipartimento di Chimica e Chimica Industriale, University of Pisa ,
  • Veronica Macaluso Dipartimento di Chimica e Chimica Industriale, University of Pisa ,
  • Giulia Pellicci Dipartimento di Chimica e Chimica Industriale, University of Pisa ,
  • Lorenzo Cupellini Dipartimento di Chimica e Chimica Industriale, University of Pisa ,
  • Giovanni Granucci Dipartimento di Chimica e Chimica Industriale, University of Pisa ,
  • Benedetta Mennucci Dipartimento di Chimica e Chimica Industriale, University of Pisa

Abstract

Phytochromes are ubiquitous photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of the embedded bilin chromophore, which triggers a large conformational change in the protein. The initial photoisomerization and the following structural changes propagating from the chromophore to the entire protein are controlled by a delicate interplay of interactions between the chromophore and the protein residues. Although the numerous studies, the molecular details of this control remain elusive. Here, we apply an integrated computational approach that combines non-adiabatic and adiabatic molecular dynamics simulations to the Deinococcus radiodurans bacteriophytochrome. Our simulations show that the photoisomerization of the chromophore proceeds through a hula-twist mechanism whose kinetics is mainly determined by the hydrogen-bonding interaction of the chromophore with a close-by histidine. The resulting photoproduct rapidly relaxes in an early intermediate thanks to a stabilizing effect of a tyrosine, and finally evolves into a late intermediate, characterized by a more disordered binding pocket and a weakening of the aspartate-to-arginine salt-bridge interaction, whose cleavage is essential to interconvert the phytochrome to the final active state.

Version notes

We have improved our manuscript with additional analyses and a more in-depth discussion of our work in the context of the experimental and computational literature. We have focused this new version on the role of the environment in the phytochromes’ photoactivation. In particular, we have analyzed the role of the residues in determining the barrier around one of the "reactive" dihedrals for the photoisomerization and further tested the robustness of the results with respect to the parameters used in the surface hopping simulations.

Content

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Supplementary material

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Supplementary Information
Selection of the QM semiempirical method; Computational details on the set-up of the non-adiabatic/adiabatic molecular dynamics simulations; Clustering details; Computational details on the IR spectroscopy simulation; Supplementary Figures.
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Supplementary Movie
Each dot represents a trajectory in the conformational space defined by the dihedrals D5 and D6. In this video only some representative trajectories are represented. The left panel represents the first electronic excited state of the biliverdin chromophore, while the right panel the ground state. Blue dots are the reactive trajectories, while the orange dots are the non-reactive trajectories.