Understanding the folding-function tradeoff in proteins.
When an amino-acid sequence cannot be optimized for both folding and function, folding can get compromised in favor of function. To understand this tradeoff better, we devise a novel method for extracting the "function-less" folding-motif of a protein fold from a set of structurally simila...
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Public Library of Science (PLoS)
2013
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oai:doaj.org-article:9fce7457630b4658bb8102ba9f797c932021-11-18T07:49:35ZUnderstanding the folding-function tradeoff in proteins.1932-620310.1371/journal.pone.0061222https://doaj.org/article/9fce7457630b4658bb8102ba9f797c932013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23593437/?tool=EBIhttps://doaj.org/toc/1932-6203When an amino-acid sequence cannot be optimized for both folding and function, folding can get compromised in favor of function. To understand this tradeoff better, we devise a novel method for extracting the "function-less" folding-motif of a protein fold from a set of structurally similar but functionally diverse proteins. We then obtain the β-trefoil folding-motif, and study its folding using structure-based models and molecular dynamics simulations. CompariA protein sequence serves two purpson with the folding of wild-type β-trefoil proteins shows that function affects folding in two ways: In the slower folding interleukin-1β, binding sites make the fold more complex, increase contact order and slow folding. In the faster folding hisactophilin, residues which could have been part of the folding-motif are used for function. This reduces the density of native contacts in functional regions and increases folding rate. The folding-motif helps identify subtle structural deviations which perturb folding. These may then be used for functional annotation. Further, the folding-motif could potentially be used as a first step in the sequence design of function-less scaffold proteins. Desired function can then be engineered into these scaffolds.Shachi GosaviPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e61222 (2013) |
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Medicine R Science Q |
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Medicine R Science Q Shachi Gosavi Understanding the folding-function tradeoff in proteins. |
| description |
When an amino-acid sequence cannot be optimized for both folding and function, folding can get compromised in favor of function. To understand this tradeoff better, we devise a novel method for extracting the "function-less" folding-motif of a protein fold from a set of structurally similar but functionally diverse proteins. We then obtain the β-trefoil folding-motif, and study its folding using structure-based models and molecular dynamics simulations. CompariA protein sequence serves two purpson with the folding of wild-type β-trefoil proteins shows that function affects folding in two ways: In the slower folding interleukin-1β, binding sites make the fold more complex, increase contact order and slow folding. In the faster folding hisactophilin, residues which could have been part of the folding-motif are used for function. This reduces the density of native contacts in functional regions and increases folding rate. The folding-motif helps identify subtle structural deviations which perturb folding. These may then be used for functional annotation. Further, the folding-motif could potentially be used as a first step in the sequence design of function-less scaffold proteins. Desired function can then be engineered into these scaffolds. |
| format |
article |
| author |
Shachi Gosavi |
| author_facet |
Shachi Gosavi |
| author_sort |
Shachi Gosavi |
| title |
Understanding the folding-function tradeoff in proteins. |
| title_short |
Understanding the folding-function tradeoff in proteins. |
| title_full |
Understanding the folding-function tradeoff in proteins. |
| title_fullStr |
Understanding the folding-function tradeoff in proteins. |
| title_full_unstemmed |
Understanding the folding-function tradeoff in proteins. |
| title_sort |
understanding the folding-function tradeoff in proteins. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/9fce7457630b4658bb8102ba9f797c93 |
| work_keys_str_mv |
AT shachigosavi understandingthefoldingfunctiontradeoffinproteins |
| _version_ |
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