dorsal/arxiv
View SchemaSimulation, Experiment, and Evolution: Understanding Nucleation in Protein S6 Folding
| Authors | Isaac Hubner, Mikael Oliveberg, Eugene Shakhnovich |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0404038 |
| URL | https://arxiv.org/abs/q-bio/0404038 |
| DOI | 10.1073/pnas.0401672101 |
Abstract
In this study, we explore nucleation and the transition state ensemble of the ribosomal protein S6 using a Monte Carlo Go model in conjunction with restraints from experiment. The results are analyzed in the context of extensive experimental and evolutionary data. The roles of individual residues in the folding nucleus are identified and the order of events in the S6 folding mechanism is explored in detail. Interpretation of our results agrees with, and extends the utility of, experiments that shift f-values by modulating denaturant concentration and presents strong evidence for the realism of the mechanistic details in our Monte Carlo Go model and the structural interpretation of experimental f-values. We also observe plasticity in the contacts of the hydrophobic core that support the specific nucleus. For S6, which binds to RNA and protein after folding, this plasticity may result from the conformational flexibility required to achieve biological function. These results present a theoretical and conceptual picture that is relevant in understanding the mechanism of nucleation in protein folding.
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"abstract": "In this study, we explore nucleation and the transition state ensemble of the\nribosomal protein S6 using a Monte Carlo Go model in conjunction with\nrestraints from experiment. The results are analyzed in the context of\nextensive experimental and evolutionary data. The roles of individual residues\nin the folding nucleus are identified and the order of events in the S6 folding\nmechanism is explored in detail. Interpretation of our results agrees with, and\nextends the utility of, experiments that shift f-values by modulating\ndenaturant concentration and presents strong evidence for the realism of the\nmechanistic details in our Monte Carlo Go model and the structural\ninterpretation of experimental f-values. We also observe plasticity in the\ncontacts of the hydrophobic core that support the specific nucleus. For S6,\nwhich binds to RNA and protein after folding, this plasticity may result from\nthe conformational flexibility required to achieve biological function. These\nresults present a theoretical and conceptual picture that is relevant in\nunderstanding the mechanism of nucleation in protein folding.",
"arxiv_id": "q-bio/0404038",
"authors": [
"Isaac Hubner",
"Mikael Oliveberg",
"Eugene Shakhnovich"
],
"categories": [
"q-bio.BM",
"cond-mat.soft"
],
"doi": "10.1073/pnas.0401672101",
"title": "Simulation, Experiment, and Evolution: Understanding Nucleation in Protein S6 Folding",
"url": "https://arxiv.org/abs/q-bio/0404038"
},
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