dorsal/arxiv
View SchemaProtein folding in high-dimensional spaces:hypergutters and the role of non-native interactions
| Authors | T. C. B. McLeish |
|---|---|
| Categories | |
| ArXiv ID | physics/0311028 |
| URL | https://arxiv.org/abs/physics/0311028 |
Abstract
We explore the consequences of very high dimensionality in the dynamical landscape of protein folding. Consideration of both typical range of stabilising interactions, and folding rates themselves, leads to a model of the energy hypersurface that is characterised by the structure of diffusive "hypergutters" as well as the familiar "funnels". Several general predictions result: (1) intermediate subspaces of configurations will always be visited; (2) specific but non-native interactions are important in stabilising these low-dimensional diffusive searches on the folding pathway; (3) sequential barriers will commonly be found, even in "two-state"proteins; (4) very early times will show charactreristic departures from single-exponential kinetics; (5) contributions of non-native interactions to phi-values are calculable, and may be significant. The example of a three-helix bundle is treated in more detail as an illustration. The model also shows that high-dimensional structures provide conceptual relations between the "folding funnel", "diffusion-collision", "nucleation-condensation" and "topomer search" models of protein folding. It suggests that kinetic strategies for fast folding may be encoded rather generally in non-native, rather than native interactions. The predictions are related to very recent findings in experiment and simulation.
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"abstract": "We explore the consequences of very high dimensionality in the dynamical\nlandscape of protein folding. Consideration of both typical range of\nstabilising interactions, and folding rates themselves, leads to a model of the\nenergy hypersurface that is characterised by the structure of diffusive\n\"hypergutters\" as well as the familiar \"funnels\". Several general predictions\nresult: (1) intermediate subspaces of configurations will always be visited;\n(2) specific but non-native interactions are important in stabilising these\nlow-dimensional diffusive searches on the folding pathway; (3) sequential\nbarriers will commonly be found, even in \"two-state\"proteins; (4) very early\ntimes will show charactreristic departures from single-exponential kinetics;\n(5) contributions of non-native interactions to phi-values are calculable, and\nmay be significant. The example of a three-helix bundle is treated in more\ndetail as an illustration. The model also shows that high-dimensional\nstructures provide conceptual relations between the \"folding funnel\",\n\"diffusion-collision\", \"nucleation-condensation\" and \"topomer search\" models of\nprotein folding. It suggests that kinetic strategies for fast folding may be\nencoded rather generally in non-native, rather than native interactions. The\npredictions are related to very recent findings in experiment and simulation.",
"arxiv_id": "physics/0311028",
"authors": [
"T. C. B. McLeish"
],
"categories": [
"physics.bio-ph",
"q-bio.BM"
],
"title": "Protein folding in high-dimensional spaces:hypergutters and the role of non-native interactions",
"url": "https://arxiv.org/abs/physics/0311028"
},
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