Multiscale Approach to the Determination of the Photoactive Yellow Protein Signaling State Ensemble

Mary A. Rohrdanz, Wenwei Zheng, Bradley Lambeth, Jocelyne Vreede, Cecilia Clementi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The nature of the optical cycle of photoactive yellow protein (PYP) makes its elucidation challenging for both experiment and theory. The long transition times render conventional simulation methods ineffective, and yet the short signaling-state lifetime makes experimental data difficult to obtain and interpret. Here, through an innovative combination of computational methods, a prediction and analysis of the biological signaling state of PYP is presented. Coarse-grained modeling and locally scaled diffusion map are first used to obtain a rough bird's-eye view of the free energy landscape of photo-activated PYP. Then all-atom reconstruction, followed by an enhanced sampling scheme; diffusion map-directed-molecular dynamics are used to focus in on the signaling-state region of configuration space and obtain an ensemble of signaling state structures. To the best of our knowledge, this is the first time an all-atom reconstruction from a coarse grained model has been performed in a relatively unexplored region of molecular configuration space. We compare our signaling state prediction with previous computational and more recent experimental results, and the comparison is favorable, which validates the method presented. This approach provides additional insight to understand the PYP photo cycle, and can be applied to other systems for which more direct methods are impractical.

Original languageEnglish (US)
JournalPLoS Computational Biology
Volume10
Issue number10
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Ensemble
Proteins
Protein
protein
Configuration Space
proteins
molecular conformation
Molecular Conformation
prediction
molecular dynamics
Molecular Dynamics Simulation
Cycle
Lifetime Data
Atoms
methodology
Energy Landscape
Prediction
Computational methods
Direct Method
Molecular Dynamics

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Cite this

Multiscale Approach to the Determination of the Photoactive Yellow Protein Signaling State Ensemble. / A. Rohrdanz, Mary; Zheng, Wenwei; Lambeth, Bradley; Vreede, Jocelyne; Clementi, Cecilia.

In: PLoS Computational Biology, Vol. 10, No. 10, 01.01.2014.

Research output: Contribution to journalArticle

A. Rohrdanz, Mary ; Zheng, Wenwei ; Lambeth, Bradley ; Vreede, Jocelyne ; Clementi, Cecilia. / Multiscale Approach to the Determination of the Photoactive Yellow Protein Signaling State Ensemble. In: PLoS Computational Biology. 2014 ; Vol. 10, No. 10.
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