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The Role of Non-Native Interactions in the Folding of Knotted Proteins: Insights from Molecular Dynamics Simulations
Department of Physics, University of Trento, Via Sommarive 14, Trento 38123, Italy
INFN-TIFPA, Trento Institute for Fundamental Physics and Applications, Trento 38123, Italy
SISSA—Scuola Internazionale Superiore di Studi Avanzati, Via Bonomea 265, Trieste 34136, Italy
Physics and Astronomy Department, University of Padua, Via Marzolo 8, Padova 35131, Italy
Interdisciplinary Laboratory for Computational Science, FBK-CMM and University of Trento,Trento 38123, Italy
* Author to whom correspondence should be addressed.
Received: 6 November 2013; in revised form: 10 December 2013 / Accepted: 20 December 2013 / Published: 24 December 2013
Abstract: For several decades, the presence of knots in naturally-occurring proteins was largely ruled out a priori for its supposed incompatibility with the efficiency and robustness of folding processes. For this very same reason, the later discovery of several unrelated families of knotted proteins motivated researchers to look into the physico-chemical mechanisms governing the concerted sequence of folding steps leading to the consistent formation of the same knot type in the same protein location. Besides experiments, computational studies are providing considerable insight into these mechanisms. Here, we revisit a number of such recent investigations within a common conceptual and methodological framework. By considering studies employing protein models with different structural resolution (coarse-grained or atomistic) and various force fields (from pure native-centric to realistic atomistic ones), we focus on the role of native and non-native interactions. For various unrelated instances of knotted proteins, non-native interactions are shown to be very important for favoring the emergence of conformations primed for successful self-knotting events.
Keywords: knotted proteins; folding simulations; non-native interactions
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Covino, R.; Škrbić, T.; Beccara, S.A.; Faccioli, P.; Micheletti, C. The Role of Non-Native Interactions in the Folding of Knotted Proteins: Insights from Molecular Dynamics Simulations. Biomolecules 2014, 4, 1-19.
Covino R, Škrbić T, Beccara SA, Faccioli P, Micheletti C. The Role of Non-Native Interactions in the Folding of Knotted Proteins: Insights from Molecular Dynamics Simulations. Biomolecules. 2014; 4(1):1-19.
Covino, Roberto; Škrbić, Tatjana; Beccara, Silvio A.; Faccioli, Pietro; Micheletti, Cristian. 2014. "The Role of Non-Native Interactions in the Folding of Knotted Proteins: Insights from Molecular Dynamics Simulations." Biomolecules 4, no. 1: 1-19.