Folding with a protein's native shortcut network
نویسنده
چکیده
The physical basis of shortcut edges in a Protein Residue Network (PRN) and their applicability to a simplified protein folding pathway problem are investigated. The results show promise and suggest the dominant influence of native-state topology even for structurally homologous proteins with different preferred folding pathways. Shortcut edges are enriched with hydrogen bonds, and there is a significant strong negative correlation between their relative contact order and the relative folding rates of 44 small and structurally diverse proteins. The initial folding reaction points identified for several single-domain proteins including LB1, GB1, and GB1's two variants NuG1 and NuG2 by the clustering coefficient computed on the ShortCut Network (SCN), are in agreement with experimental and theoretical evidence. Influence of the native SCN could be traced in non-native structures on folding trajectories of the Villin Headpiece subdomain. Significantly, the influence is stronger in structures on the more successful folding trajectories. Also observed, but with PRNs, is that key folding sites for the proteins examined have more rigid profiles.
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