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DC Field | Value | Language |
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dc.contributor.author | Cho, E | - |
dc.contributor.author | Rosa, M | - |
dc.contributor.author | Anjum, R | - |
dc.contributor.author | Mehmood, S | - |
dc.contributor.author | Soban, M | - |
dc.contributor.author | Mujtaba, M | - |
dc.contributor.author | Bux, K | - |
dc.contributor.author | Dantu, S | - |
dc.contributor.author | Pandini, A | - |
dc.contributor.author | Yin, J | - |
dc.contributor.author | Ma, H | - |
dc.contributor.author | Ramanathan, A | - |
dc.contributor.author | Islam, B | - |
dc.contributor.author | Mey, ASJS | - |
dc.contributor.author | Bhowmik, D | - |
dc.contributor.author | Haider, S | - |
dc.date.accessioned | 2023-05-07T17:58:41Z | - |
dc.date.available | 2023-05-07T17:58:41Z | - |
dc.date.issued | 2021-04-09 | - |
dc.identifier | ORCID iDs: Sarath Dantu https://orcid.org/0000-0003-2019-5311; Barira Islam https://orcid.org/0000-0001-5882-6903; Antonia S J S Mey https://orcid.org/0000-0001-7512-5252; Debsindhu Bhowmik https://orcid.org/0000-0001-7770-9091; Shozeb Haider https://orcid.org/0000-0003-2650-2925. | - |
dc.identifier.citation | Cho, E. et al. (2021) 'Structural dynamics of the β-coronavirus M<sup>pro</sup> protease ligand binding sites', BiorXiv, Preprint, pp. 1 - 42. doi: 10.1101/2021.03.31.437918. (This article is a preprint and has not been certified by peer review). | en_US |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/26413 | - |
dc.description | This article is a preprint and has not been certified by peer review. It was eventually published online on 14 June 2021 by American Chemical Society (ACS Publications) as: Cho, E. et al. (2021) 'Dynamic Profiling of β-Coronavirus 3CL Mpro Protease Ligand-Binding Sites', Journal of Chemical Information and Modeling, 61 (6), pp. 3058 - 3073. doi: 10.1021/acs.jcim.1c00449. | en_US |
dc.description | Data Availability Statement: The trajectories of Mpro simulations and models of the metastable states can be obtained from the corresponding author. Jupyter-notebooks to generate Markov State Models can be downloaded from 10.6084/m9.figshare.14343725 | - |
dc.description | bioRxiv posts many COVID19-related papers. A reminder: they have not been formally peer-reviewed and should not guide health-related behavior or be reported in the press as conclusive. | - |
dc.description.abstract | β-coronaviruses alone have been responsible for three major global outbreaks in the 21st century. The current crisis has led to an urgent requirement to develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components are required as a back-up against the emergence of lethal viral variants. One such target is the main protease (Mpro) that plays an indispensible role in viral replication. The availability of over 270 Mpro X-ray structures in complex with inhibitors provides unique insights into ligand-protein interactions. Herein, we provide a comprehensive comparison of all non-redundant ligand-binding sites available for SARS-CoV2, SARS-CoV and MERS-CoV Mpro. Extensive adaptive sampling has been used to explore conformational dynamics employing convolutional variational auto encoder-based deep learning, and investigates structural conservation of the ligand binding sites using Markov state models across β-coronavirus homologs. Our results indicate that not all ligand-binding sites are dynamically conserved despite high sequence and structural conservation across β-coronavirus homologs. This highlights the complexity in targeting all three Mpro enzymes with a single pan inhibitor. | en_US |
dc.description.sponsorship | U.S. Department of Energy, Office of Science, through the Advanced Scientific Computing Research (ASCR), under contract number DEAC05-00OR22725 and the Exascale Computing Project (ECP) (17-SC-20-SC). BI would like to acknowledge the COVID-19 pump-priming grant from the University of Huddersfield for funding computing resources for analysis. | en_US |
dc.format.extent | 1 - 42 | - |
dc.format.medium | Electronic | - |
dc.language.iso | en_US | en_US |
dc.publisher | Cold Spring Harbor Laboratory | en_US |
dc.relation.uri | https://pubs.acs.org/doi/10.1021/acs.jcim.1c00449# | - |
dc.title | Structural dynamics of the β-coronavirus M<sup>pro</sup> protease ligand binding sites | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.1101/2021.03.31.437918 | - |
dc.identifier.eissn | 2692-8205 | - |
Appears in Collections: | Dept of Computer Science Research Papers |
Files in This Item:
File | Description | Size | Format | |
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Preprint.pdf | 16.28 MB | Adobe PDF | View/Open |
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