Directionality in protein fold prediction

Ellis, Jonathan J., Huard, Fabien P. E., Deane, Charlotte M., Srivastava, Sheenal and Wood, Graham R. (2010) Directionality in protein fold prediction. Bmc Bioinformatics, 11 Article # 172: . doi:10.1186/1471-2105-11-172


Author Ellis, Jonathan J.
Huard, Fabien P. E.
Deane, Charlotte M.
Srivastava, Sheenal
Wood, Graham R.
Title Directionality in protein fold prediction
Journal name Bmc Bioinformatics   Check publisher's open access policy
ISSN 1471-2105
Publication date 2010-04-01
Sub-type Article (original research)
DOI 10.1186/1471-2105-11-172
Open Access Status DOI
Volume 11
Issue Article # 172
Total pages 16
Place of publication London, Engalnd, U.K.
Publisher BioMed Central
Language eng
Formatted abstract
Background: Ever since the ground-breaking work of Anfinsen et al. in which a denatured protein was found to refold to its native state, it has been frequently stated by the protein fold prediction community that all the information required for protein folding lies in the amino acid sequence. Recent in vitro experiments and in silico computational studies, however, have shown that cotranslation may affect the folding pathway of some proteins, especially those of ancient folds. In this paper aspects of cotranslational folding have been incorporated into a protein structure prediction algorithm by adapting the Rosetta program to fold proteins as the nascent chain elongates. This makes it possible to conduct a pairwise comparison of folding accuracy, by comparing folds created sequentially from each end of the protein.Results: A single main result emerged: in 94% of proteins analyzed, following the sense of translation, from N-terminus to C-terminus, produced better predictions than following the reverse sense of translation, from the C-terminus to N-terminus. Two secondary results emerged. First, this superiority of N-terminus to C-terminus folding was more marked for proteins showing stronger evidence of cotranslation and second, an algorithm following the sense of translation produced predictions comparable to, and occasionally better than, Rosetta.Conclusions: There is a directionality effect in protein fold prediction. At present, prediction methods appear to be too noisy to take advantage of this effect; as techniques refine, it may be possible to draw benefit from a sequential approach to protein fold prediction.
Keyword Nascent Chain
In-Vivo
Molecular Chaperones
Escherichia-Coli
Capsid Protein
Trigger Factor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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