Proteins Breaking Bad: A Free Energy Perspective
| Autor: | Ionel Popa, Julio M. Fernandez, Jessica Valle-Orero, Rafael Tapia-Rojo, Jaime Andrés Rivas-Pardo, Edward C. Eckels |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemistry Energy landscape Nanotechnology 01 natural sciences Article Oxidative damage 03 medical and health sciences 030104 developmental biology 0103 physical sciences Tissue elasticity Biophysics Brownian dynamics General Materials Science Protein folding Histone octamer Physical and Theoretical Chemistry 010306 general physics Hydrophobic collapse |
| Zdroj: | The journal of physical chemistry letters. 8(15) |
| ISSN: | 1948-7185 |
| Popis: | Protein ageing may manifest as a mechanical disease that compromises tissue elasticity. As proved recently, while proteins respond to changes in force with an instantaneous elastic recoil followed by a folding contraction, aged proteins break bad, becoming unstructured polymers. Here, we explain this phenomenon in the context of a free energy model, predicting the changes in the folding landscape of proteins upon oxidative ageing. Our findings validate that protein folding under force is constituted by two separable components, polymer properties and hydrophobic collapse, and demonstrate that the latter becomes irreversibly blocked by oxidative damage. We run Brownian dynamics simulations on the landscape of protein L octamer, reproducing all experimental observables, for a naïve and damaged polyprotein. This work provides a unique tool to understand the evolving free energy landscape of elastic proteins upon physiological changes, opening new perspectives to predict age-related diseases in tissues. |
| Databáze: | OpenAIRE |
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