Examining a Thermodynamic Order Parameter of Protein Folding

Abstract Dimensionality reduction with a suitable choice of order parameters or reaction coordinates is commonly used for analyzing high-dimensional time-series data generated by atomistic biomolecular simulations. So far, geometric order parameters, such as the root mean square deviation, fraction...

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Autores principales:	Song-Ho Chong, Sihyun Ham
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b8ac930d62a04b28b920b951af500cbb
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id	oai:doaj.org-article:b8ac930d62a04b28b920b951af500cbb
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spelling	oai:doaj.org-article:b8ac930d62a04b28b920b951af500cbb2021-12-02T12:31:56ZExamining a Thermodynamic Order Parameter of Protein Folding10.1038/s41598-018-25406-82045-2322https://doaj.org/article/b8ac930d62a04b28b920b951af500cbb2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25406-8https://doaj.org/toc/2045-2322Abstract Dimensionality reduction with a suitable choice of order parameters or reaction coordinates is commonly used for analyzing high-dimensional time-series data generated by atomistic biomolecular simulations. So far, geometric order parameters, such as the root mean square deviation, fraction of native amino acid contacts, and collective coordinates that best characterize rare or large conformational transitions, have been prevailing in protein folding studies. Here, we show that the solvent-averaged effective energy, which is a thermodynamic quantity but unambiguously defined for individual protein conformations, serves as a good order parameter of protein folding. This is illustrated through the application to the folding-unfolding simulation trajectory of villin headpiece subdomain. We rationalize the suitability of the effective energy as an order parameter by the funneledness of the underlying protein free energy landscape. We also demonstrate that an improved conformational space discretization is achieved by incorporating the effective energy. The most distinctive feature of this thermodynamic order parameter is that it works in pointing to near-native folded structures even when the knowledge of the native structure is lacking, and the use of the effective energy will also find applications in combination with methods of protein structure prediction.Song-Ho ChongSihyun HamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Song-Ho Chong Sihyun Ham Examining a Thermodynamic Order Parameter of Protein Folding
description	Abstract Dimensionality reduction with a suitable choice of order parameters or reaction coordinates is commonly used for analyzing high-dimensional time-series data generated by atomistic biomolecular simulations. So far, geometric order parameters, such as the root mean square deviation, fraction of native amino acid contacts, and collective coordinates that best characterize rare or large conformational transitions, have been prevailing in protein folding studies. Here, we show that the solvent-averaged effective energy, which is a thermodynamic quantity but unambiguously defined for individual protein conformations, serves as a good order parameter of protein folding. This is illustrated through the application to the folding-unfolding simulation trajectory of villin headpiece subdomain. We rationalize the suitability of the effective energy as an order parameter by the funneledness of the underlying protein free energy landscape. We also demonstrate that an improved conformational space discretization is achieved by incorporating the effective energy. The most distinctive feature of this thermodynamic order parameter is that it works in pointing to near-native folded structures even when the knowledge of the native structure is lacking, and the use of the effective energy will also find applications in combination with methods of protein structure prediction.
format	article
author	Song-Ho Chong Sihyun Ham
author_facet	Song-Ho Chong Sihyun Ham
author_sort	Song-Ho Chong
title	Examining a Thermodynamic Order Parameter of Protein Folding
title_short	Examining a Thermodynamic Order Parameter of Protein Folding
title_full	Examining a Thermodynamic Order Parameter of Protein Folding
title_fullStr	Examining a Thermodynamic Order Parameter of Protein Folding
title_full_unstemmed	Examining a Thermodynamic Order Parameter of Protein Folding
title_sort	examining a thermodynamic order parameter of protein folding
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/b8ac930d62a04b28b920b951af500cbb
work_keys_str_mv	AT songhochong examiningathermodynamicorderparameterofproteinfolding AT sihyunham examiningathermodynamicorderparameterofproteinfolding
_version_	1718394237094985728

Examining a Thermodynamic Order Parameter of Protein Folding

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