scholarly journals Experimental validation of free-energy-landscape reconstruction from non-equilibrium single-molecule force spectroscopy measurements

2011 ◽  
Vol 7 (8) ◽  
pp. 631-634 ◽  
Author(s):  
Amar Nath Gupta ◽  
Abhilash Vincent ◽  
Krishna Neupane ◽  
Hao Yu ◽  
Feng Wang ◽  
...  
Keyword(s):  
Free Energy ◽  
Single Molecule ◽  
Experimental Validation ◽  
Energy Landscape ◽  
Force Spectroscopy ◽  
Free Energy Landscape ◽  
Single Molecule Force Spectroscopy ◽  
Landscape Reconstruction ◽  
Non Equilibrium

scholarly journals Experimental Validation of Free Energy Landscape Reconstructions from Non-Equilibrium Single-Molecule Pulling Experiments

2011 ◽  
Vol 100 (3) ◽  
pp. 484a
Author(s):  
Abhilash Vincent ◽  
Amar Nath Gupta ◽  
Krishna Neupane ◽  
Hao Yu ◽  
Michael Woodside
Keyword(s):  
Free Energy ◽  
Single Molecule ◽  
Experimental Validation ◽  
Energy Landscape ◽  
Free Energy Landscape ◽  
Non Equilibrium

scholarly journals REFOLDING OF HOMOPOLYMER UNDER QUENCHED FORCE

2018 ◽  
Vol 55 (6A) ◽  
pp. 1
Author(s):  
Maksim Kouza
Keyword(s):  
Free Energy ◽  
Single Molecule ◽  
Energy Landscape ◽  
Coarse Grain ◽  
Free Energy Landscape ◽  
Single Molecule Force Spectroscopy ◽  
Denatured State ◽  
Dna And Rna ◽  
Go Model ◽  
The Impact

Recently single molecule force spectroscopy has become an useful tool to study protein, DNA and RNA. However, very little attention was paid to homopolymer which plays an important role in many domains of science. In this paper we make the first attempt to decipher the free energy landscape of homopolymer using the external force as reaction coordinate. The impact of the quenched force on the free energy landscape was studied using simplified coarse-grain Go model. Similar to protein, we have obtained a clear switch from the thermal regime to force-driven regime. The distance between the denatured state and transition state in the temperature-driven regime is smaller than in the force-driven one.  Having a rugged free energy landscape without a pronounced funnel the homopolymer folding is much slower than that of protein making study of homopolymer very time consuming.

scholarly journals Single-molecule force spectroscopy reveals folding steps associated with hormone binding and activation of the glucocorticoid receptor

2018 ◽  
Vol 115 (46) ◽  
pp. 11688-11693 ◽  
Author(s):  
Thomas Suren ◽  
Daniel Rutz ◽  
Patrick Mößmer ◽  
Ulrich Merkel ◽  
Johannes Buchner ◽  
...  
Keyword(s):  
Free Energy ◽  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Optical Tweezers ◽  
Single Molecule ◽  
Mechanical Load ◽  
Force Spectroscopy ◽  
Folding Pathway ◽  
Hormone Binding ◽  
Single Molecule Force Spectroscopy

The glucocorticoid receptor (GR) is a prominent nuclear receptor linked to a variety of diseases and an important drug target. Binding of hormone to its ligand binding domain (GR-LBD) is the key activation step to induce signaling. This process is tightly regulated by the molecular chaperones Hsp70 and Hsp90 in vivo. Despite its importance, little is known about GR-LBD folding, the ligand binding pathway, or the requirement for chaperone regulation. In this study, we have used single-molecule force spectroscopy by optical tweezers to unravel the dynamics of the complete pathway of folding and hormone binding of GR-LBD. We identified a “lid” structure whose opening and closing is tightly coupled to hormone binding. This lid is located at the N terminus without direct contacts to the hormone. Under mechanical load, apo-GR-LBD folds stably and readily without the need of chaperones with a folding free energy of 41 kBT (24 kcal/mol). The folding pathway is largely independent of the presence of hormone. Hormone binds only in the last step and lid closure adds an additional 12 kBT of free energy, drastically increasing the affinity. However, mechanical double-jump experiments reveal that, at zero force, GR-LBD folding is severely hampered by misfolding, slowing it to less than 1·s−1. From the force dependence of the folding rates, we conclude that the misfolding occurs late in the folding pathway. These features are important cornerstones for understanding GR activation and its tight regulation by chaperones.

scholarly journals Slow domain reconfiguration causes power-law kinetics in a two-state enzyme

2018 ◽  
Vol 115 (3) ◽  
pp. 513-518 ◽  
Author(s):  
Iris Grossman-Haham ◽  
Gabriel Rosenblum ◽  
Trishool Namani ◽  
Hagen Hofmann
Keyword(s):  
Free Energy ◽  
Single Molecule ◽  
Power Law ◽  
Energy Landscape ◽  
Rate Equations ◽  
Free Energy Landscape ◽  
Closed Domain ◽  
Single Molecule Fret ◽  
Power Law Kinetics ◽  
Interdomain Interactions

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.

Single-molecule force spectroscopy reveals signatures of glassy dynamics in the energy landscape of ubiquitin

2006 ◽  
Vol 2 (4) ◽  
pp. 282-286 ◽  
Author(s):  
Jasna Brujić ◽  
Rodolfo I. Hermans Z. ◽  
Kirstin A. Walther ◽  
Julio M. Fernandez
Keyword(s):  
Single Molecule ◽  
Energy Landscape ◽  
Force Spectroscopy ◽  
Glassy Dynamics ◽  
Single Molecule Force Spectroscopy

scholarly journals Reconstructing the free-energy landscape of a polyprotein by single-molecule experiments

2008 ◽  
Vol 82 (5) ◽  
pp. 58006 ◽  
Author(s):  
A. Imparato ◽  
F. Sbrana ◽  
M. Vassalli
Keyword(s):  
Free Energy ◽  
Single Molecule ◽  
Energy Landscape ◽  
Free Energy Landscape

scholarly journals pH-Dependent Deformations of the Energy Landscape of Avidin-like Proteins Investigated by Single Molecule Force Spectroscopy

Molecules ◽  
2014 ◽  
Vol 19 (8) ◽  
pp. 12531-12546 ◽  
Author(s):  
Melanie Köhler ◽  
Andreas Karner ◽  
Michael Leitner ◽  
Vesa Hytönen ◽  
Markku Kulomaa ◽  
...  
Keyword(s):  
Single Molecule ◽  
Energy Landscape ◽  
Force Spectroscopy ◽  
Single Molecule Force Spectroscopy ◽  
Ph Dependent
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