Variation of free‐energy landscape of the p53 C‐terminal domain induced by acetylation: Enhanced conformational sampling

Iida, Shinji; Mashimo, Tadaaki; Kurosawa, Takashi; Hojo, Hironobu; Muta, Hiroya; Goto, Yuji; Fukunishi, Yoshifumi; Haruki, Nakamura; Junichi, Higo

doi:https://doi.org/10.1002/jcc.24494

アクセス数:288件（2024-04-25 13:38 集計）

固定URL: https://hdl.handle.net/11094/71263

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タイトル	Variation of free‐energy landscape of the p53 C‐terminal domain induced by acetylation: Enhanced conformational sampling
著者	著者名 Iida, Shinji
	著者名 Mashimo, Tadaaki
	著者名 Kurosawa, Takashi
	NRID 1000000209214 1000000209214 researchmap permalink read0014254 read0014254 Scopus Author ID 7102337557 7102337557 著者名 Hojo, Hironobu
	著者名 Muta, Hiroya
	NRID 1000040153770 1000040153770 researchmap permalink read0014440 read0014440 著者名 Goto, Yuji
	NRID 1000060357895 1000060357895 著者名 Fukunishi, Yoshifumi
	NRID 1000080134485 1000080134485 著者名 Haruki, Nakamura
	NRID 1000080265719 1000080265719 著者名 Junichi, Higo
キーワード等	free energy landscape
	p53 C‐terminal
	intrinsically disordered
	post‐translation modification
	multicanonical
内容	Shinji Iida, Tadaaki Mashimo, Takashi Kurosawa, Hironobu Hojo, Hiroya Muta, Yuji Goto, Yoshifumi Fukunishi, Haruki Nakamura, and Junichi Higo, "Variation of free‐energy landscape of the p53 C‐terminal domain induced by acetylation: Enhanced conformational sampling", Journal of Computational Chemistry, 37, 2687-2700, Wiley, 2016
抄録	The C‐terminal domain (CTD) of tumor suppressor protein p53 is an intrinsically disordered region that binds to various partner proteins, where lysine of CTD is acetylated/nonacetylated and histidine neutralized/non‐neutralized. Because of the flexibility of the unbound CTD, a free‐energy landscape (FEL) is a useful quantity for determining its statistical properties. We conducted enhanced conformational sampling of CTD in the unbound state via virtual system coupled multicanonical molecular dynamics, in which the lysine was acetylated or nonacetylated and histidine was charged or neutralized. The fragments were expressed by an all‐atom model and were immersed in an explicit solvent. The acetylation and charge‐neutralization varied FEL greatly, which might be convenient to exert a hub property. The acetylation slightly enhanced alpha‐helix structures that are more compact than sheet/loop conformations. The charge‐neutralization produced hairpins. Additionally, circular dichroism experiments confirmed the computational results. We propose possible binding mechanisms of CTD to partners by investigating FEL.
出版者	Wiley
収録物名	Journal of Computational Chemistry
巻(号)	37(31)
ページ	2687-2700
刊行年月	2016-10
言語	英語
ハンドルURL	https://hdl.handle.net/11094/71263
eISSN	1096987X
NCID	AA11623124
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1002/jcc.24494
アクセス権	open access
権利情報	© 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Computational Chemistry. 2016, 37(31), p. 2687-2700
DC.title	Variation of free‐energy landscape of the p53 C‐terminal domain induced by acetylation: Enhanced conformational sampling
DC.creator	Iida, Shinji
	Mashimo, Tadaaki
	Kurosawa, Takashi
	Hojo, Hironobu
	Muta, Hiroya
	Goto, Yuji
	Fukunishi, Yoshifumi
	Haruki, Nakamura
	Junichi, Higo
DC.publisher	Wiley
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2016-10
DC.identifier	https://doi.org/10.1002/jcc.24494
DC.subject	free energy landscape
	p53 C‐terminal
	intrinsically disordered
	post‐translation modification
	multicanonical
DC.description	Shinji Iida, Tadaaki Mashimo, Takashi Kurosawa, Hironobu Hojo, Hiroya Muta, Yuji Goto, Yoshifumi Fukunishi, Haruki Nakamura, and Junichi Higo, "Variation of free‐energy landscape of the p53 C‐terminal domain induced by acetylation: Enhanced conformational sampling", Journal of Computational Chemistry, 37, 2687-2700, Wiley, 2016
DCTERMS.abstract	The C‐terminal domain (CTD) of tumor suppressor protein p53 is an intrinsically disordered region that binds to various partner proteins, where lysine of CTD is acetylated/nonacetylated and histidine neutralized/non‐neutralized. Because of the flexibility of the unbound CTD, a free‐energy landscape (FEL) is a useful quantity for determining its statistical properties. We conducted enhanced conformational sampling of CTD in the unbound state via virtual system coupled multicanonical molecular dynamics, in which the lysine was acetylated or nonacetylated and histidine was charged or neutralized. The fragments were expressed by an all‐atom model and were immersed in an explicit solvent. The acetylation and charge‐neutralization varied FEL greatly, which might be convenient to exert a hub property. The acetylation slightly enhanced alpha‐helix structures that are more compact than sheet/loop conformations. The charge‐neutralization produced hairpins. Additionally, circular dichroism experiments confirmed the computational results. We propose possible binding mechanisms of CTD to partners by investigating FEL.
DC.rights	© 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
DC.format	application/pdf
citation_title	Variation of free‐energy landscape of the p53 C‐terminal domain induced by acetylation: Enhanced conformational sampling
citation_author	Iida, Shinji
	Mashimo, Tadaaki
	Kurosawa, Takashi
	Hojo, Hironobu
	Muta, Hiroya
	Goto, Yuji
	Fukunishi, Yoshifumi
	Haruki, Nakamura
	Junichi, Higo
citation_publisher	Wiley
citation_language	英語
citation_date	2016-10
citation_journal_title	Journal of Computational Chemistry
citation_volume	37
citation_issue	31
citation_firstpage	2687
citation_lastpage	2700
citation_doi	https://doi.org/10.1002/jcc.24494
citation_public_url	https://hdl.handle.net/11094/71263

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