Protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.

Large-scale conformational changes are essential for proteins to function properly. Given that these transition events rarely occur, however, it is challenging to comprehend their underlying mechanisms through experimental and theoretical approaches. In this study, we propose a new computational met...

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Autores principales:	Byung Ho Lee, Soon Woo Park, Soojin Jo, Moon Ki Kim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/636c5faef7994d18bc8c8691cf025feb
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id	oai:doaj.org-article:636c5faef7994d18bc8c8691cf025feb
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spelling	oai:doaj.org-article:636c5faef7994d18bc8c8691cf025feb2021-12-02T20:04:23ZProtein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.1932-620310.1371/journal.pone.0258818https://doaj.org/article/636c5faef7994d18bc8c8691cf025feb2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258818https://doaj.org/toc/1932-6203Large-scale conformational changes are essential for proteins to function properly. Given that these transition events rarely occur, however, it is challenging to comprehend their underlying mechanisms through experimental and theoretical approaches. In this study, we propose a new computational methodology called internal coordinate normal mode-guided elastic network interpolation (ICONGENI) to predict conformational transition pathways in proteins. Its basic approach is to sample intermediate conformations by interpolating the interatomic distance between two end-point conformations with the degrees of freedom constrained by the low-frequency dynamics afforded by normal mode analysis in internal coordinates. For validation of ICONGENI, it is applied to proteins that undergo open-closed transitions, and the simulation results (i.e., simulated transition pathways) are compared with those of another technique, to demonstrate that ICONGENI can explore highly reliable pathways in terms of thermal and chemical stability. Furthermore, we generate an ensemble of transition pathways through ICONGENI and investigate the possibility of using this method to reveal the transition mechanisms even when there are unknown metastable states on rough energy landscapes.Byung Ho LeeSoon Woo ParkSoojin JoMoon Ki KimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0258818 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Byung Ho Lee Soon Woo Park Soojin Jo Moon Ki Kim Protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.
description	Large-scale conformational changes are essential for proteins to function properly. Given that these transition events rarely occur, however, it is challenging to comprehend their underlying mechanisms through experimental and theoretical approaches. In this study, we propose a new computational methodology called internal coordinate normal mode-guided elastic network interpolation (ICONGENI) to predict conformational transition pathways in proteins. Its basic approach is to sample intermediate conformations by interpolating the interatomic distance between two end-point conformations with the degrees of freedom constrained by the low-frequency dynamics afforded by normal mode analysis in internal coordinates. For validation of ICONGENI, it is applied to proteins that undergo open-closed transitions, and the simulation results (i.e., simulated transition pathways) are compared with those of another technique, to demonstrate that ICONGENI can explore highly reliable pathways in terms of thermal and chemical stability. Furthermore, we generate an ensemble of transition pathways through ICONGENI and investigate the possibility of using this method to reveal the transition mechanisms even when there are unknown metastable states on rough energy landscapes.
format	article
author	Byung Ho Lee Soon Woo Park Soojin Jo Moon Ki Kim
author_facet	Byung Ho Lee Soon Woo Park Soojin Jo Moon Ki Kim
author_sort	Byung Ho Lee
title	Protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.
title_short	Protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.
title_full	Protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.
title_fullStr	Protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.
title_full_unstemmed	Protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.
title_sort	protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/636c5faef7994d18bc8c8691cf025feb
work_keys_str_mv	AT byungholee proteinconformationaltransitionsexploredbyamorphingapproachbasedonnormalmodeanalysisininternalcoordinates AT soonwoopark proteinconformationaltransitionsexploredbyamorphingapproachbasedonnormalmodeanalysisininternalcoordinates AT soojinjo proteinconformationaltransitionsexploredbyamorphingapproachbasedonnormalmodeanalysisininternalcoordinates AT moonkikim proteinconformationaltransitionsexploredbyamorphingapproachbasedonnormalmodeanalysisininternalcoordinates
_version_	1718375605804728320

Protein conformational transitions explored by a morphing approach based on normal mode analysis in internal coordinates.

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