dorsal/arxiv
View SchemaNucleation phenomena in protein folding: The modulating role of protein sequence
| Authors | R. D. M. Travasso, P. F. N. Faisca, M. M. Telo da Gama |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0611061 |
| URL | https://arxiv.org/abs/q-bio/0611061 |
| DOI | 10.1088/0953-8984/19/28/285212 |
| Journal | J. Physics: Condensed Matter 19 (2007) 285212 |
Abstract
For the vast majority of naturally occurring, small, single domain proteins folding is often described as a two-state process that lacks detectable intermediates. This observation has often been rationalized on the basis of a nucleation mechanism for protein folding whose basic premise is the idea that after completion of a specific set of contacts forming the so-called folding nucleus the native state is achieved promptly. Here we propose a methodology to identify folding nuclei in small lattice polymers and apply it to the study of protein molecules with chain length N=48. To investigate the extent to which protein topology is a robust determinant of the nucleation mechanism we compare the nucleation scenario of a native-centric model with that of a sequence specific model sharing the same native fold. To evaluate the impact of the sequence's finner details in the nucleation mechanism we consider the folding of two non- homologous sequences. We conclude that in a sequence-specific model the folding nucleus is, to some extent, formed by the most stable contacts in the protein and that the less stable linkages in the folding nucleus are solely determined by the fold's topology. We have also found that independently of protein sequence the folding nucleus performs the same `topological' function. This unifying feature of the nucleation mechanism results from the residues forming the folding nucleus being distributed along the protein chain in a similar and well-defined manner that is determined by the fold's topological features.
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"abstract": "For the vast majority of naturally occurring, small, single domain proteins\nfolding is often described as a two-state process that lacks detectable\nintermediates. This observation has often been rationalized on the basis of a\nnucleation mechanism for protein folding whose basic premise is the idea that\nafter completion of a specific set of contacts forming the so-called folding\nnucleus the native state is achieved promptly. Here we propose a methodology to\nidentify folding nuclei in small lattice polymers and apply it to the study of\nprotein molecules with chain length N=48. To investigate the extent to which\nprotein topology is a robust determinant of the nucleation mechanism we compare\nthe nucleation scenario of a native-centric model with that of a sequence\nspecific model sharing the same native fold. To evaluate the impact of the\nsequence\u0027s finner details in the nucleation mechanism we consider the folding\nof two non- homologous sequences. We conclude that in a sequence-specific model\nthe folding nucleus is, to some extent, formed by the most stable contacts in\nthe protein and that the less stable linkages in the folding nucleus are solely\ndetermined by the fold\u0027s topology. We have also found that independently of\nprotein sequence the folding nucleus performs the same `topological\u0027 function.\nThis unifying feature of the nucleation mechanism results from the residues\nforming the folding nucleus being distributed along the protein chain in a\nsimilar and well-defined manner that is determined by the fold\u0027s topological\nfeatures.",
"arxiv_id": "q-bio/0611061",
"authors": [
"R. D. M. Travasso",
"P. F. N. Faisca",
"M. M. Telo da Gama"
],
"categories": [
"q-bio.BM"
],
"doi": "10.1088/0953-8984/19/28/285212",
"journal_ref": "J. Physics: Condensed Matter 19 (2007) 285212",
"title": "Nucleation phenomena in protein folding: The modulating role of protein sequence",
"url": "https://arxiv.org/abs/q-bio/0611061"
},
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