Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/152748
Title: Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data
Authors: Zhu, Guanhua
Pan, Ankita
Grüber, Gerhard
Lu, Lanyuan
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Zhu, G., Pan, A., Grüber, G. & Lu, L. (2019). Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data. Progress in Biophysics and Molecular Biology, 143, 13-19. https://dx.doi.org/10.1016/j.pbiomolbio.2018.09.005
Project: MOE2012-T3-1-008
Journal: Progress in biophysics and molecular biology
Abstract: Zika virus (ZIKV) has become a great public health emergency. Its non-structural protein 3 (NS3) is a key enzyme in viral replication and has been considered as a potential therapeutic target. A conformational characterization of ZIKV NS3 is critical for a comprehensive understanding of its molecular interactions and functions. However, the high conformational flexibility of solution NS3 obstacles the structural characterization of NS3 solely from the experimental observable that averages over its heterogeneous conformations. Here, we employed replica exchange with solute tempering (REST) method to simulate the di-domain protein ZIKV NS3. Three independent MD simulations identified a conserved conformational ensemble of NS3, consisting of a major conformational state and several minor states from compact to loose conformations. The major state agrees well with the scattering profile from small-angle X-ray scattering (SAXS) experiments. Moreover, the simulated ensemble is supported by a direct data-fitting result that requires both short- and long-range structural contacts to recover the experimental data. We discussed the interplay between simulation and experiment in ensemble construction of flexible biomolecules and shed light on the physically derived conformational ensembles.
URI: https://hdl.handle.net/10356/152748
ISSN: 0079-6107
DOI: 10.1016/j.pbiomolbio.2018.09.005
Rights: © 2018 Elsevier Ltd. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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