Effects of knots on protein folding properties.
This work explores the impact of knots, knot depth and motif of the threading terminus in protein folding properties (kinetics, thermodynamics and mechanism) via extensive Monte Carlo simulations of lattice models. A knotted backbone has no effect on protein thermodynamic stability but it may affect...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3762781?pdf=render |
| _version_ | 1818311517235314688 |
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| author | Miguel A Soler Patrícia F N Faísca |
| author_facet | Miguel A Soler Patrícia F N Faísca |
| author_sort | Miguel A Soler |
| collection | DOAJ |
| description | This work explores the impact of knots, knot depth and motif of the threading terminus in protein folding properties (kinetics, thermodynamics and mechanism) via extensive Monte Carlo simulations of lattice models. A knotted backbone has no effect on protein thermodynamic stability but it may affect key aspects of folding kinetics. In this regard, we found clear evidence for a functional advantage of knots: knots enhance kinetic stability because a knotted protein unfolds at a distinctively slower rate than its unknotted counterpart. However, an increase in knot deepness does not necessarily lead to more effective changes in folding properties. In this regard, a terminus with a non-trivial conformation (e.g. hairpin) can have a more dramatic effect in enhancing kinetic stability than knot depth. Nevertheless, our results suggest that the probability of the denatured ensemble to keep knotted is higher for proteins with deeper knots, indicating that knot depth plays a role in determining the topology of the denatured state. Refolding simulations starting from denatured knotted conformations show that not every knot is able to nucleate folding and further indicate that the formation of the knotting loop is a key event in the folding of knotted trefoils. They also show that there are specific native contacts within the knotted core that are crucial to keep a native knotting loop in denatured conformations which otherwise have no detectable structure. The study of the knotting mechanism reveals that the threading of the knotting loop generally occurs towards late folding in conformations that exhibit a significant degree of structural consolidation. |
| first_indexed | 2024-12-13T08:03:13Z |
| format | Article |
| id | doaj.art-79cd98e8bf88407981dea66e5e1802bf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T08:03:13Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-79cd98e8bf88407981dea66e5e1802bf2022-12-21T23:54:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7475510.1371/journal.pone.0074755Effects of knots on protein folding properties.Miguel A SolerPatrícia F N FaíscaThis work explores the impact of knots, knot depth and motif of the threading terminus in protein folding properties (kinetics, thermodynamics and mechanism) via extensive Monte Carlo simulations of lattice models. A knotted backbone has no effect on protein thermodynamic stability but it may affect key aspects of folding kinetics. In this regard, we found clear evidence for a functional advantage of knots: knots enhance kinetic stability because a knotted protein unfolds at a distinctively slower rate than its unknotted counterpart. However, an increase in knot deepness does not necessarily lead to more effective changes in folding properties. In this regard, a terminus with a non-trivial conformation (e.g. hairpin) can have a more dramatic effect in enhancing kinetic stability than knot depth. Nevertheless, our results suggest that the probability of the denatured ensemble to keep knotted is higher for proteins with deeper knots, indicating that knot depth plays a role in determining the topology of the denatured state. Refolding simulations starting from denatured knotted conformations show that not every knot is able to nucleate folding and further indicate that the formation of the knotting loop is a key event in the folding of knotted trefoils. They also show that there are specific native contacts within the knotted core that are crucial to keep a native knotting loop in denatured conformations which otherwise have no detectable structure. The study of the knotting mechanism reveals that the threading of the knotting loop generally occurs towards late folding in conformations that exhibit a significant degree of structural consolidation.http://europepmc.org/articles/PMC3762781?pdf=render |
| spellingShingle | Miguel A Soler Patrícia F N Faísca Effects of knots on protein folding properties. PLoS ONE |
| title | Effects of knots on protein folding properties. |
| title_full | Effects of knots on protein folding properties. |
| title_fullStr | Effects of knots on protein folding properties. |
| title_full_unstemmed | Effects of knots on protein folding properties. |
| title_short | Effects of knots on protein folding properties. |
| title_sort | effects of knots on protein folding properties |
| url | http://europepmc.org/articles/PMC3762781?pdf=render |
| work_keys_str_mv | AT miguelasoler effectsofknotsonproteinfoldingproperties AT patriciafnfaisca effectsofknotsonproteinfoldingproperties |