Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data
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 molecula...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/152748 |
| _version_ | 1826130438575357952 |
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| author | Zhu, Guanhua Pan, Ankita Grüber, Gerhard Lu, Lanyuan |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Zhu, Guanhua Pan, Ankita Grüber, Gerhard Lu, Lanyuan |
| author_sort | Zhu, Guanhua |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T07:56:30Z |
| format | Journal Article |
| id | ntu-10356/152748 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:56:30Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1527482021-09-23T04:48:41Z Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data Zhu, Guanhua Pan, Ankita Grüber, Gerhard Lu, Lanyuan School of Biological Sciences Science::Biological sciences Zika Virus Non-structural Protein 3 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. Ministry of Education (MOE) This research is supported by the Tier 3 grant (MOE2012-T3-1- 008) from the Ministry of Education, Singapore. 2021-09-23T04:48:40Z 2021-09-23T04:48:40Z 2019 Journal Article 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 0079-6107 https://hdl.handle.net/10356/152748 10.1016/j.pbiomolbio.2018.09.005 30291845 2-s2.0-85065803881 143 13 19 en MOE2012-T3-1-008 Progress in biophysics and molecular biology © 2018 Elsevier Ltd. All rights reserved. |
| spellingShingle | Science::Biological sciences Zika Virus Non-structural Protein 3 Zhu, Guanhua Pan, Ankita Grüber, Gerhard Lu, Lanyuan Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data |
| title | Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data |
| title_full | Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data |
| title_fullStr | Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data |
| title_full_unstemmed | Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data |
| title_short | Conformational states of Zika virus non-structural protein 3 determined by molecular dynamics simulations with small-angle X-Ray scattering data |
| title_sort | conformational states of zika virus non structural protein 3 determined by molecular dynamics simulations with small angle x ray scattering data |
| topic | Science::Biological sciences Zika Virus Non-structural Protein 3 |
| url | https://hdl.handle.net/10356/152748 |
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