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dc.contributor.authorShimada, Jun
dc.contributor.authorShakhnovich, Eugene I.
dc.date.accessioned2019-10-11T12:29:15Z
dc.date.issued2002
dc.identifier.citationShimada, J., and E. I. Shakhnovich. 2002. “The Ensemble Folding Kinetics of Protein G from an All-Atom Monte Carlo Simulation.” Proceedings of the National Academy of Sciences99 (17): 11175–80. https://doi.org/10.1073/pnas.162268099.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41534415*
dc.description.abstractProtein G is folded with an all-atom Monte Carlo simulation by using a Go potential. When folding is monitored by using burial of the lone tryptophan in protein G as the reaction coordinate, the ensemble kinetics is single exponential. Other experimental observations, such as the burst phase and mutational data, are also reproduced. However, more detailed analysis reveals that folding occurs over three distinct, three-state pathways. We show that, because of this tryptophan's asymmetric location in the tertiary fold, its burial (i) does not detect certain intermediates and (h) may not correspond to the folding event. This finding demonstrates that ensemble averaging can disguise the presence of multiple pathways and intermediates when a non-ideal reaction coordinate is used. Finally, all observed folding pathways eventually converge to a common rate-limiting step, which is the formation of a specific nucleus involving hydrophobic core residues. These residues are conserved in the ubiquitin superfamily and in a phage display experiment, suggesting that fold topology is a strong determinant of the transition state.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleThe ensemble folding kinetics of protein G from an all-atom Monte Carlo simulation
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorShakhnovich, Eugene Isaacovitch::f6c3b099a5c771576073eb9a31658d2e::600
dc.date.available2019-10-11T12:29:15Z
dash.workflow.comments1Science Serial ID 89452
dc.identifier.doi10.1073/pnas.162268099
dash.source.volume99;17
dash.source.page11175


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