Thermal versus Mechanical Unfolding in a Model Protein
| Autor: | Fernando Falo, Juan J. Mazo, Rafael Tapia-Rojo |
|---|---|
| Přispěvatelé: | Agencia Estatal de Investigación (España), Ministerio de Economía, Industria y Competitividad (España), Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Gobierno de Aragón, European Commission, FENOL, Tapia-Rojo, R. [0000-0002-9460-2859], Mazo, J. J. [0000-0003-0698-6555], Falo, Fernando [0000-0002-9551-624X], Tapia-Rojo, R., Mazo, J. J., Falo, Fernando |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Protein Conformation General Physics and Astronomy Non-equilibrium thermodynamics 010402 general chemistry Space (mathematics) 01 natural sciences Reaction coordinate Metastability 0103 physical sciences Thermal Statistical physics Physical and Theoretical Chemistry Mechanical Phenomena Protein Unfolding Physics Quantitative Biology::Biomolecules 010304 chemical physics Markov chain Temperature Force spectroscopy Proteins Energy landscape Markov Chains 0104 chemical sciences Folding (chemistry) |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2014-5586 |
| DOI: | 10.1101/816801 |
| Popis: | Force spectroscopy techniques are often used to learn about the free energy landscape of single biomolecules, typically by recovering free energy quantities that, extrapolated to zero force, are compared to those measured in bulk experiments. However, it is not always clear how the information obtained from a mechanically perturbed system can be related to the information obtained using other denaturants since tensioned molecules unfold and refold along a reaction coordinate imposed by the force, which is not likely to be meaningful in its absence. Here, we explore this dichotomy by investigating the unfolding landscape of a model protein, which is unfolded first mechanically through typical force spectroscopy-like protocols and next thermally. When unfolded by nonequilibrium force extension and constant force protocols, we recover a simple two-barrier landscape as the protein reaches the extended conformation through a metastable intermediate. Interestingly, folding-unfolding equilibrium simulations at low forces suggested a totally different scenario, where this metastable state plays little role in the unfolding mechanism, and the protein unfolds through two competing pathways [R. Tapia-Rojo et al., J. Chem. Phys. 141, 135102 (2014)]. Finally, we use Markov state models to describe the configurational space of the unperturbed protein close to the critical temperature. The thermal dynamics is well understood by a one-dimensional landscape along an appropriate reaction coordinate, however it is very different from the mechanical picture. In this sense, the results of our protein model for the mechanical and thermal descriptions provide incompatible views of the folding/unfolding landscape of the system, and the estimated quantities to zero force result are hard to interpret. This work was supported by Spanish Ministerio de Economía, Industria y Competitividad (MINECO) (Project Nos. FIS2014-55867-P and FIS2017-87519-P), cofinanced by the Fondo Europeo de Desarrollo Regional (FEDER), and by the Gobierno de Aragón, Grant to the FENOL group, Grant No. E36_17R. |
| Databáze: | OpenAIRE |
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