dvunkannon
Posts: 1377
Joined: June 2008
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| Quote (REC @ June 15 2010,16:02) | | Quote (dvunkannon @ June 15 2010,14:49) | A query to y'all sciency types:
I was reading Nick Lane's "The 10 Great Inventions of Evolution" last week. At one point he is describing the historical path to understanding how RNA led to protein formation, and the realization that amino acids didn't just attach to random spots on the mRNA chain, instead the ribsome mediated the growth of the protein as it walked the length of the messenger RNA.
I was suddenly struck by the question of whether any protein folding algorithm actually works the same the way the ribosome does.
My general impression of ab initio protein folding algorithms is that they start with the whole linear string of peptides floating freely in a solvent, and then let the whole string twist and collapse under the influence of local force fields. They don't, to my knowledge, build up the protein one AA at a time from one end which is tethered to a large object (ribosome + mRNA). Not surprisingly, they often don't fold into the native conformation.
Reinforcing my general impression, a google search on 'incremental protein folding algorithm' didn't generate any decent hits.
So I ask you - do you know of any such algorithm? Is this an idea that has been tried and discarded? It would seem to me to be much faster in some ways. Any suggestions on where/who could provide better insights? |
The search you're looking for is "algorithm cotranslational protein folding"
Since co-translational folding is a known (but fought over) mechanism, that makes solution folding of a whole denatured protein and the folding of a nascent peptide during translation different, this is important.
http://www.jbc.org/content/275/22/16597.full
And people are starting to work on it:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523309/
"Molecular Simulations of Cotranslational Protein Folding: Fragment Stabilities, Folding Cooperativity, and Trapping in the Ribosome" |
Thanks, REC!
From a recent publication:
| Quote | BMC Bioinformatics. 2010 Apr 7;11:172.
Directionality in protein fold prediction.
Ellis JJ, Huard FP, Deane CM, Srivastava S, Wood GR.
Department of Statistics, Macquarie University, Sydney, NSW 2109, Australia.
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. |
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I’m referring to evolution, not changes in allele frequencies. - Cornelius Hunter
I’m not an evolutionist, I’m a change in allele frequentist! - Nakashima
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