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

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

© 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

Bibliographische Detailangaben
Veröffentlicht in:Journal of computational chemistry. - 1984. - 37(2016), 31 vom: 05. Dez., Seite 2687-2700
1. Verfasser: Iida, Shinji (VerfasserIn)
Weitere Verfasser: Mashimo, Tadaaki, Kurosawa, Takashi, Hojo, Hironobu, Muta, Hiroya, Goto, Yuji, Fukunishi, Yoshifumi, Nakamura, Haruki, Higo, Junichi
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Journal of computational chemistry
Schlagworte:Journal Article Research Support, Non-U.S. Gov't free energy landscape intrinsically disordered multicanonical p53 C-terminal post-translation modification Tumor Suppressor Protein p53
Beschreibung
Zusammenfassung:© 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
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. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc
Beschreibung:Date Completed 24.07.2018
Date Revised 23.05.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1096-987X
DOI:10.1002/jcc.24494