Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
27
pubmed:dateCreated
2008-7-1
pubmed:abstractText
The principle of microscopic reversibility states that at equilibrium the number of molecules entering a state by a given path must equal those exiting the state via the same path under identical conditions or, in structural terms, that the conformations along the two pathways are the same. There has been some indirect evidence indicating that protein folding is such a process, but there have been few conclusive findings. In this study, we performed molecular dynamics simulations of an ultrafast unfolding and folding protein at its melting temperature to observe, on an atom-by-atom basis, the pathways the protein followed as it unfolded and folded within a continuous trajectory. In a total of 0.67 micros of simulation in water, we found six transient denaturing events near the melting temperature (323 and 330 K) and an additional refolding event following a previously identified unfolding event at a high temperature (373 K). In each case, unfolding and refolding transition state ensembles were identified, and they agreed well with experiment on the basis of a comparison of S and Phi values. On the basis of several structural properties, these 13 transition state ensembles agreed very well with each other and with four previously identified transition states from high-temperature denaturing simulations. Thus, not only were the unfolding and refolding transition states part of the same ensemble, but in five of the seven cases, the pathway the protein took as it unfolded was nearly identical to the subsequent refolding pathway. These events provide compelling evidence that protein folding is a microscopically reversible process. In the other two cases, the folding and unfolding transition states were remarkably similar to each other but the paths deviated.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-10438631, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-11087839, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-12215424, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-12594518, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-14583194, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-14595026, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-15264254, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-15283920, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-15328620, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-15641786, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-15840831, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-16587035, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-17174331, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-17978165, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-1977522, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-7490748, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-7756312, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-7937969, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-8218192, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-8609634, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-8744570, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-9466940, http://linkedlifedata.com/resource/pubmed/commentcorrection/18553935-9813123
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7079-89
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Microscopic reversibility of protein folding in molecular dynamics simulations of the engrailed homeodomain.
pubmed:affiliation
Biomolecular Structure and Design Program, University of Washington, Box 355013, Seattle, Washington 98195-5013, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural