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| Autori principali: | , , , , |
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| Natura: | Preprint |
| Pubblicazione: |
2025
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| Accesso online: | https://arxiv.org/abs/2511.07024 |
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| _version_ | 1866915855665725440 |
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| author | Especial, João N. C. Teixeira, Beatriz P. Nunes, Ana Machuqueiro, Miguel Faísca, Patrícia F. N. |
| author_facet | Especial, João N. C. Teixeira, Beatriz P. Nunes, Ana Machuqueiro, Miguel Faísca, Patrícia F. N. |
| contents | For several decades, experimental and computational studies have been used to investigate the potential functional role of knots in protein structures. A property that has attracted considerable attention is thermal stability, i.e., the extent to which a protein retains its native conformation and biological activity at high temperatures, without undergoing denaturation or aggregation. Thermal stability is quantified by the melting temperature Tm, an equilibrium property that corresponds to the peak of heat capacity in differential scanning calorimetry (DSC) experiments. Experimental and computational studies report conflicting effects of knotting on protein thermal stability. Here, we use extensive Monte Carlo simulations of a simple C-alpha model of protein YibK, with energetics modeled by the Go potential, to show that Tm does not depend on the topological state of the protein. Our simulations further support the view that the discrepancy between the experimental and computational results stems from a pronounced separation of timescales for unknotting and unfolding that is inherent to deeply knotted proteins like YibK. In particular, the timescale separation implies that the complete unfolding-untying transition may not be accessible within the duration of a DSC experiment, whose apparent Tm measurements likely reflect a non-equilibrium distribution lacking unfolded states that are also unknotted. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2511_07024 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | The role of topology on protein thermal stability Especial, João N. C. Teixeira, Beatriz P. Nunes, Ana Machuqueiro, Miguel Faísca, Patrícia F. N. Biomolecules For several decades, experimental and computational studies have been used to investigate the potential functional role of knots in protein structures. A property that has attracted considerable attention is thermal stability, i.e., the extent to which a protein retains its native conformation and biological activity at high temperatures, without undergoing denaturation or aggregation. Thermal stability is quantified by the melting temperature Tm, an equilibrium property that corresponds to the peak of heat capacity in differential scanning calorimetry (DSC) experiments. Experimental and computational studies report conflicting effects of knotting on protein thermal stability. Here, we use extensive Monte Carlo simulations of a simple C-alpha model of protein YibK, with energetics modeled by the Go potential, to show that Tm does not depend on the topological state of the protein. Our simulations further support the view that the discrepancy between the experimental and computational results stems from a pronounced separation of timescales for unknotting and unfolding that is inherent to deeply knotted proteins like YibK. In particular, the timescale separation implies that the complete unfolding-untying transition may not be accessible within the duration of a DSC experiment, whose apparent Tm measurements likely reflect a non-equilibrium distribution lacking unfolded states that are also unknotted. |
| title | The role of topology on protein thermal stability |
| topic | Biomolecules |
| url | https://arxiv.org/abs/2511.07024 |