Extracting the underlying effective free energy landscape from single-molecule time series—local equilibrium states and their network

2011 ◽  
Vol 13 (4) ◽  
pp. 1395-1406 ◽  
Author(s):  
Akinori Baba ◽  
Tamiki Komatsuzaki
2018 ◽  
Vol 115 (3) ◽  
pp. 513-518 ◽  
Author(s):  
Iris Grossman-Haham ◽  
Gabriel Rosenblum ◽  
Trishool Namani ◽  
Hagen Hofmann

Protein dynamics are typically captured well by rate equations that predict exponential decays for two-state reactions. Here, we describe a remarkable exception. The electron-transfer enzyme quiescin sulfhydryl oxidase (QSOX), a natural fusion of two functionally distinct domains, switches between open- and closed-domain arrangements with apparent power-law kinetics. Using single-molecule FRET experiments on time scales from nanoseconds to milliseconds, we show that the unusual open-close kinetics results from slow sampling of an ensemble of disordered domain orientations. While substrate accelerates the kinetics, thus suggesting a substrate-induced switch to an alternative free energy landscape of the enzyme, the power-law behavior is also preserved upon electron load. Our results show that the slow sampling of open conformers is caused by a variety of interdomain interactions that imply a rugged free energy landscape, thus providing a generic mechanism for dynamic disorder in multidomain enzymes.


Biopolymers ◽  
2008 ◽  
Vol 89 (7) ◽  
pp. 565-577 ◽  
Author(s):  
James B. Munro ◽  
Andrea Vaiana ◽  
Kevin Y. Sanbonmatsu ◽  
Scott C. Blanchard

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