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J Mol Model. 2018 Apr 24;24(5):113. doi: 10.1007/s00894-018-3643-6.

Exploration of nucleoprotein α-MoRE and XD interactions of Nipah and Hendra viruses.

Author information

1
College of Physics, Jilin University, Changchun, 130012, China.
2
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.
3
IMDEA-Nanociencia, Campus Cantoblanco, Madrid, 28049, Spain.
4
Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257, CNRS and Aix-Marseille University, Marseille, France.
5
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China. jin.wang.1@stonybrook.edu.
6
Department of Chemistry & Physics, State University of New York at Stony Brook, Stony Brook, NY, 11794, USA. jin.wang.1@stonybrook.edu.

Abstract

Henipavirus, including Hendra virus (HeV) and Nipah virus (NiV), is a newly discovered human pathogen genus. The nucleoprotein of Henipavirus contains an α-helical molecular recognition element (α-MoRE) that folds upon binding to the X domain (XD) of the phosphoprotein (P). In order to explore the conformational dynamics of free α-MoREs and the underlying binding-folding mechanism with XD, atomic force field-based and hybrid structure-based MD simulations were carried out. In our empirical force field-based simulations, characteristic structures and helicities of α-MoREs reveal the co-existence of partially structured and disordered conformations, as in the case of the well characterized cognate measles virus (MeV) α-MoRE. In spite of their overall similarity, the two α-MoREs display subtle helicity differences in their C-terminal region, but much different from that of MeV. For the α-MoRE/XD complexes, the results of our hybrid structure-based simulations provide the coupled binding-folding landscapes, and unveil a wide conformational selection mechanism at early binding stages, followed by a final induce-fit mechanism selection process. However, the HeV and NiV complexes have a lower binding barrier compared to that of MeV. Moreover, the HeV α-MoRE/XD complex shows much less coupling effects between binding and folding compared to that from both NiV and MeV. Our analysis revealed that contrary to NiV and MeV, the N- and C-terminal regions of the HeV α-MoRE maintains a low helicity also in the bound form.

KEYWORDS:

Coupled binding-folding; Free energy landscapes; Hybrid structure-based model; IDP; α-MoREs

PMID:
29691656
DOI:
10.1007/s00894-018-3643-6
[Indexed for MEDLINE]

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