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:info:doi/10.1002/jcc.24494

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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	Iida, Shinji Iida, Shinji
	Mashimo, Tadaaki Mashimo, Tadaaki
	Kurosawa, Takashi Kurosawa, Takashi
	Hojo, Hironobu Hojo, Hironobu
	Muta, Hiroya Muta, Hiroya
	Goto, Yuji Goto, Yuji
	Fukunishi, Yoshifumi Fukunishi, Yoshifumi
	Haruki Nakamura Haruki Nakamura
	Junichi Higo 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.
公開者	Wiley
掲載誌名	Journal of Computational Chemistry
巻	37
号	31
開始ページ	2687
終了ページ	2700
刊行年月	2016-10
ISSN	1096987X
NCID	AA11623124
DOI	info:doi/10.1002/jcc.24494
URL	http://hdl.handle.net/11094/71263
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.
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII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.37(31) P.2687-P.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
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2016-10
DC.identifier	info:doi/10.1002/jcc.24494
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/71263
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.
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_issn	1096987X
citation_doi	info:doi/10.1002/jcc.24494
citation_public_url	http://hdl.handle.net/11094/71263
citation_keywords	free energy landscape
	p53 C‐terminal
	intrinsically disordered
	post‐translation modification
	multicanonical

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