Limits...
Multiscale approach to the determination of the photoactive yellow protein signaling state ensemble.

A Rohrdanz M, Zheng W, Lambeth B, Vreede J, Clementi C - PLoS Comput. Biol. (2014)

Bottom Line: The long transition times render conventional simulation methods ineffective, and yet the short signaling-state lifetime makes experimental data difficult to obtain and interpret.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Theoretical Biological Physics, Rice University, Houston, Texas, United States of America; Chemistry Department, Rice University, Houston, Texas, United States of America.

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.

Show MeSH

Related in: MedlinePlus

Comparison of the Cα deviations from the pG configuration for the experimental Δ25 configurations (PDB ID 1XFQ) in black, experimental WT-PYP pB configurations (PDB ID: 2KX6) in green, and our pB ensemble in blue.The horizontal axis is the index number relative to PYP (i.e. the first index of Δ25 is at 25 on the graph). For all three datasets, the regions of the sequence similar to the pG dark state are similar, as are most of the regions where the fluctuations are larger. The primary differences are near the chromophore (residue 69) and are discussed in the main text.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4214557&req=5

pcbi-1003797-g004: Comparison of the Cα deviations from the pG configuration for the experimental Δ25 configurations (PDB ID 1XFQ) in black, experimental WT-PYP pB configurations (PDB ID: 2KX6) in green, and our pB ensemble in blue.The horizontal axis is the index number relative to PYP (i.e. the first index of Δ25 is at 25 on the graph). For all three datasets, the regions of the sequence similar to the pG dark state are similar, as are most of the regions where the fluctuations are larger. The primary differences are near the chromophore (residue 69) and are discussed in the main text.

Mentions: Figure 4 compares the results. For regions of the protein in which the pG secondary structure is preserved in the pB state, for example the α helix formed by residues 79–84, the Cα displacement is minimal. However in regions of the protein where structure is lost, for example the α3 helix in residues 79–84, the fluctuations are larger. There is general agreement among all three datasets. The two main conserved regions are the helix in residues 76–85, and the central β sheet, and can be seen in all three signaling-state structures in Figure 3.


Multiscale approach to the determination of the photoactive yellow protein signaling state ensemble.

A Rohrdanz M, Zheng W, Lambeth B, Vreede J, Clementi C - PLoS Comput. Biol. (2014)

Comparison of the Cα deviations from the pG configuration for the experimental Δ25 configurations (PDB ID 1XFQ) in black, experimental WT-PYP pB configurations (PDB ID: 2KX6) in green, and our pB ensemble in blue.The horizontal axis is the index number relative to PYP (i.e. the first index of Δ25 is at 25 on the graph). For all three datasets, the regions of the sequence similar to the pG dark state are similar, as are most of the regions where the fluctuations are larger. The primary differences are near the chromophore (residue 69) and are discussed in the main text.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214557&req=5

pcbi-1003797-g004: Comparison of the Cα deviations from the pG configuration for the experimental Δ25 configurations (PDB ID 1XFQ) in black, experimental WT-PYP pB configurations (PDB ID: 2KX6) in green, and our pB ensemble in blue.The horizontal axis is the index number relative to PYP (i.e. the first index of Δ25 is at 25 on the graph). For all three datasets, the regions of the sequence similar to the pG dark state are similar, as are most of the regions where the fluctuations are larger. The primary differences are near the chromophore (residue 69) and are discussed in the main text.
Mentions: Figure 4 compares the results. For regions of the protein in which the pG secondary structure is preserved in the pB state, for example the α helix formed by residues 79–84, the Cα displacement is minimal. However in regions of the protein where structure is lost, for example the α3 helix in residues 79–84, the fluctuations are larger. There is general agreement among all three datasets. The two main conserved regions are the helix in residues 76–85, and the central β sheet, and can be seen in all three signaling-state structures in Figure 3.

Bottom Line: The long transition times render conventional simulation methods ineffective, and yet the short signaling-state lifetime makes experimental data difficult to obtain and interpret.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Theoretical Biological Physics, Rice University, Houston, Texas, United States of America; Chemistry Department, Rice University, Houston, Texas, United States of America.

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.

Show MeSH
Related in: MedlinePlus