Stochastic simulations of coarse-grained protein models are used to investigate the propensity to form knots in early stages of protein folding. The study is carried out comparatively for two homologous carbamoyltransferases, a natively-knotted N-acetylornithine carbamoyltransferase (AOTCase) and an unknotted ornithine carbamoyltransferase (OTCase). In addition, two different sets of pairwise amino acid interactions are considered: one promoting exclusively native interactions, and the other additionally including non-native quasi-chemical and electrostatic interactions. With the former model neither protein shows a propensity to form knots. With the additional non-native interactions, knotting propensity remains negligible for the natively-unknotted OTCase while for AOTCase it is much enhanced. Analysis of the trajectories suggests that the different entanglement of the two transcarbamylases follows from the tendency of the C-terminal to point away from (for OTCase) or approach and eventually thread (for AOTCase) other regions of partly-folded protein. The analysis of the OTCase/AOTCase pair clarifies that natively-knotted proteins can spontaneously knot during early folding stages and that non-native sequence-dependent interactions are important for promoting and disfavouring early knotting events. © 2012 Škrbić et al.
|Titolo:||The Role of Non-Native Interactions in the Folding of Knotted Proteins|
|Autori:||Skrbic, T; Micheletti, C; Faccioli, P|
|Rivista:||PLOS COMPUTATIONAL BIOLOGY|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||10.1371/journal.pcbi.1002504|
|Fulltext via DOI:||10.1371/journal.pcbi.1002504|
|Appare nelle tipologie:||1.1 Journal article|