A Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation

Calmodulin (CaM) is a multifunctional calcium-binding protein, which regulates a variety of biochemical processes. CaM acts through its conformational changes and complex formation with its target enzymes. CaM consists of two globular domains (N-lobe and C-lobe) linked by an extended linker region....

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Autores principales:	Hiromitsu Shimoyama, Yasuteru Shigeta
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	molecular dynamics simulation calmodulin domain motion dynamics conformational change free-energy analysis Science Q
Acceso en línea:	https://doaj.org/article/8e08bd4119f14d98a5aa824ad7419f9d
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spelling	oai:doaj.org-article:8e08bd4119f14d98a5aa824ad7419f9d2021-11-25T18:11:29ZA Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation10.3390/life111112412075-1729https://doaj.org/article/8e08bd4119f14d98a5aa824ad7419f9d2021-11-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1241https://doaj.org/toc/2075-1729Calmodulin (CaM) is a multifunctional calcium-binding protein, which regulates a variety of biochemical processes. CaM acts through its conformational changes and complex formation with its target enzymes. CaM consists of two globular domains (N-lobe and C-lobe) linked by an extended linker region. Upon calcium binding, the N-lobe and C-lobe undergo local conformational changes, followed by a major conformational change of the entire CaM to wrap the target enzyme. However, the regulation mechanisms, such as allosteric interactions, which regulate the large structural changes, are still unclear. In order to investigate the series of structural changes, the free-energy landscape of CaM was obtained by multi-scale divide-and-conquer molecular dynamics (MSDC-MD). The resultant free-energy landscape (FEL) shows that the Ca<sup>2+</sup> bound CaM (holo-CaM) would take an experimentally famous elongated structure, which can be formed in the early stage of structural change, by breaking the inter-domain interactions. The FEL also shows that important interactions complete the structural change from the elongated structure to the ring-like structure. In addition, the FEL might give a guiding principle to predict mutational sites in CaM. In this study, it was demonstrated that the movement process of macroscopic variables on the FEL may be diffusive to some extent, and then, the MSDC-MD is suitable to the parallel computation.Hiromitsu ShimoyamaYasuteru ShigetaMDPI AGarticlemolecular dynamics simulationcalmodulindomain motiondynamicsconformational changefree-energy analysisScienceQENLife, Vol 11, Iss 1241, p 1241 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	molecular dynamics simulation calmodulin domain motion dynamics conformational change free-energy analysis Science Q
spellingShingle	molecular dynamics simulation calmodulin domain motion dynamics conformational change free-energy analysis Science Q Hiromitsu Shimoyama Yasuteru Shigeta A Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation
description	Calmodulin (CaM) is a multifunctional calcium-binding protein, which regulates a variety of biochemical processes. CaM acts through its conformational changes and complex formation with its target enzymes. CaM consists of two globular domains (N-lobe and C-lobe) linked by an extended linker region. Upon calcium binding, the N-lobe and C-lobe undergo local conformational changes, followed by a major conformational change of the entire CaM to wrap the target enzyme. However, the regulation mechanisms, such as allosteric interactions, which regulate the large structural changes, are still unclear. In order to investigate the series of structural changes, the free-energy landscape of CaM was obtained by multi-scale divide-and-conquer molecular dynamics (MSDC-MD). The resultant free-energy landscape (FEL) shows that the Ca<sup>2+</sup> bound CaM (holo-CaM) would take an experimentally famous elongated structure, which can be formed in the early stage of structural change, by breaking the inter-domain interactions. The FEL also shows that important interactions complete the structural change from the elongated structure to the ring-like structure. In addition, the FEL might give a guiding principle to predict mutational sites in CaM. In this study, it was demonstrated that the movement process of macroscopic variables on the FEL may be diffusive to some extent, and then, the MSDC-MD is suitable to the parallel computation.
format	article
author	Hiromitsu Shimoyama Yasuteru Shigeta
author_facet	Hiromitsu Shimoyama Yasuteru Shigeta
author_sort	Hiromitsu Shimoyama
title	A Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation
title_short	A Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation
title_full	A Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation
title_fullStr	A Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation
title_full_unstemmed	A Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation
title_sort	free-energy landscape analysis of calmodulin obtained from an nmr data-utilized multi-scale divide-and-conquer molecular dynamics simulation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8e08bd4119f14d98a5aa824ad7419f9d
work_keys_str_mv	AT hiromitsushimoyama afreeenergylandscapeanalysisofcalmodulinobtainedfromannmrdatautilizedmultiscaledivideandconquermoleculardynamicssimulation AT yasuterushigeta afreeenergylandscapeanalysisofcalmodulinobtainedfromannmrdatautilizedmultiscaledivideandconquermoleculardynamicssimulation AT hiromitsushimoyama freeenergylandscapeanalysisofcalmodulinobtainedfromannmrdatautilizedmultiscaledivideandconquermoleculardynamicssimulation AT yasuterushigeta freeenergylandscapeanalysisofcalmodulinobtainedfromannmrdatautilizedmultiscaledivideandconquermoleculardynamicssimulation
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A Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation

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