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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-10-24
pubmed:abstractText
The influence of native connectivity of secondary structure elements (SSE) on folding is studied using coarse-grained models of proteins with mixed alpha and beta structure and the analysis of the structural database of wild-type proteins. We found that the distribution of SSE along a sequence determines the diversity of folding pathways. If alpha and beta SSE are localized in different parts of a sequence, the diversity of folding pathways is restricted. An even (symmetric) distribution of alpha and beta SSE with respect to sequence midpoint favors multiple folding routes. Simulations are supplemented by the database analysis of the distribution of SSE in wild-type protein sequences. On an average, two-thirds of wild-type proteins with mixed alpha and beta structure have symmetric distribution of alpha and beta SSE. The propensity for symmetric distribution of SSE is especially evident for large proteins with the number of SSE > or = 10. We suggest that symmetric SSE distribution in protein sequences may arise due to nearly random allocation of alpha and beta structure along wild-type sequences. The tendency of long sequences to misfold is perhaps compensated by the enhanced pathway diversity. In addition, folding pathways are shown to progress via hierarchic assembly of SSE in accordance with their proximity along a sequence. We demonstrate that under mild denaturation conditions folding and unfolding pathways are similar. However, the reversibility of folding/unfolding pathways is shown to depend on the distribution of SSE. If alpha and beta SSE are localized in different parts of a sequence, folding and unfolding pathways are likely to coincide.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
353
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1171-86
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Symmetric connectivity of secondary structure elements enhances the diversity of folding pathways.
pubmed:affiliation
Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University, Manassas, VA 20110, USA. dklimov@gmu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.