dorsal/arxiv
View SchemaNucleation and the transition state of the SH3 domain
| Authors | Isaac A. Hubner, Katherine A. Edmonds, Eugene I. Shakhnovich |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0503027 |
| URL | https://arxiv.org/abs/q-bio/0503027 |
Abstract
We present a verified computational model of the SH3 domain transition state (TS) ensemble. This model was built for three separate SH3 domains using experimental s in all-atom protein folding simulations. While averaging over all conformations incorrectly considers non-TS conformations as transition states, quantifying structures as pre-TS, TS, and post-TS by measurement of their transmission coefficient (pfold, or probability to fold) allows for rigorous conclusions regarding the structure of the folding nucleus and a full mechanistic analysis of the folding process. Through analysis of the TS, we observe a highly polarized nucleus in which many residues are solvent-exposed. Mechanistic analysis suggests the hydrophobic core forms largely after an early nucleation step. SH3 presents an ideal system for studying the nucleation-condensation mechanism and highlights the synergistic relationship between experiment and simulation in the study of protein folding.
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"date_created": "2026-03-02T18:01:31.155000Z",
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"abstract": "We present a verified computational model of the SH3 domain transition state\n(TS) ensemble. This model was built for three separate SH3 domains using\nexperimental s in all-atom protein folding simulations. While averaging over\nall conformations incorrectly considers non-TS conformations as transition\nstates, quantifying structures as pre-TS, TS, and post-TS by measurement of\ntheir transmission coefficient (pfold, or probability to fold) allows for\nrigorous conclusions regarding the structure of the folding nucleus and a full\nmechanistic analysis of the folding process. Through analysis of the TS, we\nobserve a highly polarized nucleus in which many residues are solvent-exposed.\nMechanistic analysis suggests the hydrophobic core forms largely after an early\nnucleation step. SH3 presents an ideal system for studying the\nnucleation-condensation mechanism and highlights the synergistic relationship\nbetween experiment and simulation in the study of protein folding.",
"arxiv_id": "q-bio/0503027",
"authors": [
"Isaac A. Hubner",
"Katherine A. Edmonds",
"Eugene I. Shakhnovich"
],
"categories": [
"q-bio.BM",
"q-bio.OT"
],
"title": "Nucleation and the transition state of the SH3 domain",
"url": "https://arxiv.org/abs/q-bio/0503027"
},
"schema_id": "dorsal/arxiv",
"source": {
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