Probing the Transition State Ensemble of a Protein Folding Reaction by Pressure-Dependent NMR Relaxation Dispersion

2006 ◽  
Vol 128 (15) ◽  
pp. 5262-5269 ◽  
Author(s):  
Dmitry M. Korzhnev ◽  
Irina Bezsonova ◽  
Ferenc Evanics ◽  
Nicolas Taulier ◽  
Zheng Zhou ◽  
...  
Keyword(s):  
Protein Folding ◽  
Transition State ◽  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
State Ensemble ◽  
Transition State Ensemble

scholarly journals Constrained proper sampling of conformations of transition state ensemble of protein folding

2011 ◽  
Vol 134 (7) ◽  
pp. 075103 ◽  
Author(s):  
Ming Lin ◽  
Jian Zhang ◽  
Hsiao-Mei Lu ◽  
Rong Chen ◽  
Jie Liang
Keyword(s):  
Protein Folding ◽  
Transition State ◽  
State Ensemble ◽  
Transition State Ensemble ◽  
Proper Sampling

scholarly journals Protein folding funnels: the nature of the transition state ensemble

1996 ◽  
Vol 1 (6) ◽  
pp. 441-450 ◽  
Author(s):  
José Nelson Onuchic ◽  
Nicholas D. Socci ◽  
Zaida Luthey-Schulten ◽  
Peter G. Wolynes
Keyword(s):  
Protein Folding ◽  
Transition State ◽  
State Ensemble ◽  
Transition State Ensemble

scholarly journals Direct Molecular Dynamics Observation of Protein Folding Transition State Ensemble

2002 ◽  
Vol 83 (6) ◽  
pp. 3525-3532 ◽  
Author(s):  
Feng Ding ◽  
Nikolay V. Dokholyan ◽  
Sergey V. Buldyrev ◽  
H. Eugene Stanley ◽  
Eugene I. Shakhnovich
Keyword(s):  
Molecular Dynamics ◽  
Protein Folding ◽  
Transition State ◽  
State Ensemble ◽  
Transition State Ensemble

scholarly journals The Volumetric Properties of the Transition State Ensemble for Protein Folding

2021 ◽  
Author(s):  
Samvel Avagyan ◽  
George Makhatadze
Keyword(s):  
Protein Folding ◽  
Hydrostatic Pressure ◽  
Transition State ◽  
Protein Unfolding ◽  
Activation Volume ◽  
Environmental Variable ◽  
Volume Changes ◽  
Biological Adaptation ◽  
State Ensemble ◽  
Transition State Ensemble

Hydrostatic pressure together with the temperature is an important environmental variable that plays an essential role in biological adaptation of extremophilic organisms. In particular, the effects of hy-drostatic pressure on the rates of the protein folding/unfolding reaction are determined by the magni-tude and sign of the activation volume changes. Here we provide computational description of the ac-tivation volume changes for folding/unfolding reaction, and compare them with the experimental data for six different globular proteins. We find that the volume of the transition state ensemble is always in-between the folded and unfolded states. Based on this, we conclude that hydrostatic pressure will invariably slow down protein folding and accelerate protein unfolding.

Mutational investigation of protein folding transition states by Φ-value analysis and beyond: lessons from SH3 domain foldingThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (2) ◽  
pp. 231-238 ◽  
Author(s):  
Arash Zarrine-Afsar ◽  
Sung Lun Lin ◽  
Philipp Neudecker
Keyword(s):  
Protein Folding ◽  
Transition State ◽  
Structural Information ◽  
Peer Review Process ◽  
Transition States ◽  
Nmr Relaxation ◽  
Relaxation Dispersion ◽  
Folding Kinetics ◽  
Value Analysis ◽  
Kinetic Effects

Understanding how proteins adopt their unique native structures requires a complete structural characterization of the rate-limiting transition state(s) along the folding pathway. By definition, transition states are not significantly populated and are only accessible via folding kinetics studies. In this respect, interpreting the kinetic effects of amino acid substitutions (especially to Ala) via Φ-value analysis is the most common method to probe the structure of these transient, yet important states. A critical review of the key assumptions required for rigorous interpretation of Φ values reveals that a multiple substitution strategy in which a position of interest is mutated to a variety of amino acids, and not exclusively to Ala, provides the best means to characterize folding transition states. This approach has proven useful in revealing non-native interactions and (or) conformations in folding transition states. Moreover, by simultaneously examining the folding kinetics of multiple substitutions made at a single surface-exposed position using the Brønsted analysis the backbone conformation in a folding transition state can be investigated. For folding equilibria with exchange rates on the order of milliseconds, the kinetic parameters for Φ-value analysis can be obtained from NMR relaxation dispersion experiments, under fully native conditions, along with a wealth of high-resolution structural information about the states in exchange (native, denatured, and intermediate states that populate the pathway). This additional structural information, which is not readily obtained through stopped-flow based methods, can significantly facilitate the interpretation of Φ values because it often reports on the validity of the assumptions required for a rigorous interpretation of Φ values.

The experimental survey of protein-folding energy landscapes

2005 ◽  
Vol 38 (3) ◽  
pp. 245-288 ◽  
Author(s):  
Mikael Oliveberg ◽  
Peter G. Wolynes
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Transition State ◽  
Energy Landscape ◽  
Energy Profile ◽  
Global Features ◽  
Value Analysis ◽  
Free Energy Profile ◽  
State Ensemble ◽  
Transition State Ensemble

1. Introduction 22. The macroscopic and microscopic views of protein folding 22.1 The macroscopic view: the experimental folding free-energy profile 22.2 The microscopic view: an underlying energy landscape 33. The micro to macro projection: from an energy landscape to a free-energy profile 64. Global features of the protein folding transition-state ensemble 124.1 Overall transition state location β[Dagger]: a measure of compactness 124.2 What makes folding so robust ? 135. Structural characterization of the transition-state ensemble 165.1 Insights from ϕ-value analysis 166. Deviations from ideality 206.1 β[Dagger] shifts along seemingly robust trajectories 216.2 Anomalous ϕ values, frustration and inhomogeneities 257. Intermediates 288. Detours, traps and frustration 298.1 Premature collapse and non-native trapping 299. Diffusion on the energy landscape and the elementary events of protein folding 3010. Malleability of folding routes: changes of the dominant collective coordinates for folding 3311. The evolution of the shape of the energy landscape 3511.1 Negative design: the hidden dimension of the folding code 3512. Mechanistic multiplicity and evolutionary choice 3613. Acknowledgements 3714. References 38We review what has been learned about the protein-folding problem from experimental kinetic studies. These studies reveal patterns of both great richness and surprising simplicity. The patterns can be interpreted in terms of proteins possessing an energy landscape which is largely, but not completely, funnel-like. Issues such as speed limitations of folding, the robustness of folding, the origin of barriers and cooperativity and the ensemble nature of transition states, intermediate and traps are assessed using the results from several experimental groups highlighting energy-landscape ideas as an interpretive framework.

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