Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins

Abstract A long time ago, Kuhn predicted that long polymers should approach a limit where their global motion is controlled by solvent friction alone, with ruggedness of their energy landscapes having no consequences for their dynamics. In contrast, internal friction effects are important for polyme...

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Autores principales:	Stanislav M. Avdoshenko, Atanu Das, Rohit Satija, Garegin A. Papoian, Dmitrii E. Makarov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3a3e22f75774b28b052c2e346b47321
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spelling	oai:doaj.org-article:f3a3e22f75774b28b052c2e346b473212021-12-02T11:53:04ZTheoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins10.1038/s41598-017-00287-52045-2322https://doaj.org/article/f3a3e22f75774b28b052c2e346b473212017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00287-5https://doaj.org/toc/2045-2322Abstract A long time ago, Kuhn predicted that long polymers should approach a limit where their global motion is controlled by solvent friction alone, with ruggedness of their energy landscapes having no consequences for their dynamics. In contrast, internal friction effects are important for polymers of modest length. Internal friction in proteins, in particular, affects how fast they fold or find their binding targets and, as such, has attracted much recent attention. Here we explore the molecular origins of internal friction in unfolded proteins using atomistic simulations, coarse-grained models and analytic theory. We show that the characteristic internal friction timescale is directly proportional to the timescale of hindered dihedral rotations within the polypeptide chain, with a proportionality coefficient b that is independent of the chain length. Such chain length independence of b provides experimentally testable evidence that internal friction arises from concerted, crankshaft-like dihedral rearrangements. In accord with phenomenological models of internal friction, we find the global reconfiguration timescale of a polypeptide to be the sum of solvent friction and internal friction timescales. At the same time, the time evolution of inter-monomer distances within polypeptides deviates both from the predictions of those models and from a simple, one-dimensional diffusion model.Stanislav M. AvdoshenkoAtanu DasRohit SatijaGaregin A. PapoianDmitrii E. MakarovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stanislav M. Avdoshenko Atanu Das Rohit Satija Garegin A. Papoian Dmitrii E. Makarov Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins
description	Abstract A long time ago, Kuhn predicted that long polymers should approach a limit where their global motion is controlled by solvent friction alone, with ruggedness of their energy landscapes having no consequences for their dynamics. In contrast, internal friction effects are important for polymers of modest length. Internal friction in proteins, in particular, affects how fast they fold or find their binding targets and, as such, has attracted much recent attention. Here we explore the molecular origins of internal friction in unfolded proteins using atomistic simulations, coarse-grained models and analytic theory. We show that the characteristic internal friction timescale is directly proportional to the timescale of hindered dihedral rotations within the polypeptide chain, with a proportionality coefficient b that is independent of the chain length. Such chain length independence of b provides experimentally testable evidence that internal friction arises from concerted, crankshaft-like dihedral rearrangements. In accord with phenomenological models of internal friction, we find the global reconfiguration timescale of a polypeptide to be the sum of solvent friction and internal friction timescales. At the same time, the time evolution of inter-monomer distances within polypeptides deviates both from the predictions of those models and from a simple, one-dimensional diffusion model.
format	article
author	Stanislav M. Avdoshenko Atanu Das Rohit Satija Garegin A. Papoian Dmitrii E. Makarov
author_facet	Stanislav M. Avdoshenko Atanu Das Rohit Satija Garegin A. Papoian Dmitrii E. Makarov
author_sort	Stanislav M. Avdoshenko
title	Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins
title_short	Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins
title_full	Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins
title_fullStr	Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins
title_full_unstemmed	Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins
title_sort	theoretical and computational validation of the kuhn barrier friction mechanism in unfolded proteins
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f3a3e22f75774b28b052c2e346b47321
work_keys_str_mv	AT stanislavmavdoshenko theoreticalandcomputationalvalidationofthekuhnbarrierfrictionmechanisminunfoldedproteins AT atanudas theoreticalandcomputationalvalidationofthekuhnbarrierfrictionmechanisminunfoldedproteins AT rohitsatija theoreticalandcomputationalvalidationofthekuhnbarrierfrictionmechanisminunfoldedproteins AT gareginapapoian theoreticalandcomputationalvalidationofthekuhnbarrierfrictionmechanisminunfoldedproteins AT dmitriiemakarov theoreticalandcomputationalvalidationofthekuhnbarrierfrictionmechanisminunfoldedproteins
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Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins

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