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The role of non-native interactions in the folding of knotted proteins.

Skrbić T, Micheletti C, Faccioli P - PLoS Comput. Biol. (2012)

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: ECT*- European Centre for Theoretical Studies in Nuclear Physics and Related Areas, Villazzano (Trento), Italy.

ABSTRACT
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.

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Monte Carlo time evolution of the average electrostatic interaction energy between the -helix and the rest of the chain, in the knotted AOTCase and unknotted OTCase.
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pcbi-1002504-g008: Monte Carlo time evolution of the average electrostatic interaction energy between the -helix and the rest of the chain, in the knotted AOTCase and unknotted OTCase.

Mentions: Finally, in Fig. 8 we plot the average electrostatic potential energy between the -helix and the rest of the chain and show that, overall, the electrostatic interaction is about two orders of magnitude smaller than that of the quasi-chemical potential.


The role of non-native interactions in the folding of knotted proteins.

Skrbić T, Micheletti C, Faccioli P - PLoS Comput. Biol. (2012)

Monte Carlo time evolution of the average electrostatic interaction energy between the -helix and the rest of the chain, in the knotted AOTCase and unknotted OTCase.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375218&req=5

pcbi-1002504-g008: Monte Carlo time evolution of the average electrostatic interaction energy between the -helix and the rest of the chain, in the knotted AOTCase and unknotted OTCase.
Mentions: Finally, in Fig. 8 we plot the average electrostatic potential energy between the -helix and the rest of the chain and show that, overall, the electrostatic interaction is about two orders of magnitude smaller than that of the quasi-chemical potential.

Bottom Line: 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 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.

View Article: PubMed Central - PubMed

Affiliation: ECT*- European Centre for Theoretical Studies in Nuclear Physics and Related Areas, Villazzano (Trento), Italy.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus