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

Iida, Shinji; Mashimo, Tadaaki; Kurosawa, Takashi et al.

Journal of Computational Chemistry, 2016, 37(31), 2687-2700

Number of Access:976（2025-08-30 13:29 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/71263

Link to primary information 

File Format Terms of use Size Views Date.Available Description information
ComChem_2016_37_2687 pdf None 1.22 MB 254 2019.02.26  
Creative Commons : Attribution

Item Information

Output File Export EndNote Basic Export Mendeley

Title
Variation of free‐energy landscape of the p53 C‐terminal domain induced by acetylation: Enhanced conformational sampling
Creator
CreatorName
Iida, Shinji
CreatorName
Mashimo, Tadaaki
CreatorName
Kurosawa, Takashi
NRID
1000000209214 1000000209214
researchmap permalink
read0014254 read0014254
Scopus Author ID
7102337557 7102337557
CreatorName
Hojo, Hironobu
CreatorName
Muta, Hiroya
NRID
1000040153770 1000040153770
researchmap permalink
read0014440 read0014440
CreatorName
Goto, Yuji
NRID
1000060357895 1000060357895
CreatorName
Fukunishi, Yoshifumi
NRID
1000080134485 1000080134485
CreatorName
Haruki, Nakamura
NRID
1000080265719 1000080265719
CreatorName
Junichi, Higo
Subject
free energy landscape
p53 C‐terminal
intrinsically disordered
post‐translation modification
multicanonical
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
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.
Publisher
Wiley
Source Title
Journal of Computational Chemistry
Volume (Issue)
37(31)
Page
2687-2700
Date of Issued
2016-10
Language
English
Handle URL
https://hdl.handle.net/11094/71263
eISSN
1096987X
NCID
AA11623124
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1002/jcc.24494
Access Rights
open access
CopyRight
© 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.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article