Modelling sequential protein folding under kinetic control
Motivation: This study presents a novel investigation of the effect of kinetic control on cotranslational protein folding. We demonstrate the effect using simple HP lattice models and show that the cotranslational folding of proteins under kinetic control has significant impact on the final conforma...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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Oxford University Press
2006
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| _version_ | 1826259692830064640 |
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| author | Huard, F Deane, C Wood, G |
| author_facet | Huard, F Deane, C Wood, G |
| author_sort | Huard, F |
| collection | OXFORD |
| description | Motivation: This study presents a novel investigation of the effect of kinetic control on cotranslational protein folding. We demonstrate the effect using simple HP lattice models and show that the cotranslational folding of proteins under kinetic control has significant impact on the final conformation. Differences arise if nature is not capable of pushing a partially folded protein back over a large energy barrier. For this reason we argue that such constraints should be incorporated into structure prediction techniques. We introduce a finite surmountable energy barrier which allows partially formed chains to partly unfold, and permits us to enumerate exhaustively all energy pathways. Results: We compare the ground states obtained sequentially with the global ground states of designing sequences (those with a unique global ground state). We find that the sequential ground states become less numerous and more compact as the surmountable energy barrier increases. We also introduce a probabilistic model to describe the distribution of final folds and allow partial settling to the Boltzmann distribution of states at each stage. As a result, conformations with the highest probability of final occurence are not necessarily the ones of lowest energy. |
| first_indexed | 2024-03-06T18:53:49Z |
| format | Journal article |
| id | oxford-uuid:1123f465-4141-4141-8b74-1bf828b49e52 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:53:49Z |
| publishDate | 2006 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:1123f465-4141-4141-8b74-1bf828b49e522022-03-26T10:00:37ZModelling sequential protein folding under kinetic controlJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1123f465-4141-4141-8b74-1bf828b49e52Statistics (see also social sciences)Mathematical genetics and bioinformatics (statistics)EnglishOxford University Research Archive - ValetOxford University Press2006Huard, FDeane, CWood, GMotivation: This study presents a novel investigation of the effect of kinetic control on cotranslational protein folding. We demonstrate the effect using simple HP lattice models and show that the cotranslational folding of proteins under kinetic control has significant impact on the final conformation. Differences arise if nature is not capable of pushing a partially folded protein back over a large energy barrier. For this reason we argue that such constraints should be incorporated into structure prediction techniques. We introduce a finite surmountable energy barrier which allows partially formed chains to partly unfold, and permits us to enumerate exhaustively all energy pathways. Results: We compare the ground states obtained sequentially with the global ground states of designing sequences (those with a unique global ground state). We find that the sequential ground states become less numerous and more compact as the surmountable energy barrier increases. We also introduce a probabilistic model to describe the distribution of final folds and allow partial settling to the Boltzmann distribution of states at each stage. As a result, conformations with the highest probability of final occurence are not necessarily the ones of lowest energy. |
| spellingShingle | Statistics (see also social sciences) Mathematical genetics and bioinformatics (statistics) Huard, F Deane, C Wood, G Modelling sequential protein folding under kinetic control |
| title | Modelling sequential protein folding under kinetic control |
| title_full | Modelling sequential protein folding under kinetic control |
| title_fullStr | Modelling sequential protein folding under kinetic control |
| title_full_unstemmed | Modelling sequential protein folding under kinetic control |
| title_short | Modelling sequential protein folding under kinetic control |
| title_sort | modelling sequential protein folding under kinetic control |
| topic | Statistics (see also social sciences) Mathematical genetics and bioinformatics (statistics) |
| work_keys_str_mv | AT huardf modellingsequentialproteinfoldingunderkineticcontrol AT deanec modellingsequentialproteinfoldingunderkineticcontrol AT woodg modellingsequentialproteinfoldingunderkineticcontrol |