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Structures of MERS-CoV Macro Domain in Aqueous Solution with Dynamics: Coupling Replica Exchange Molecular Dynamics and Deep Learning at the Nano Level
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  • Ibrahim Akbayrak ,
  • Burak Ulver ,
  • Havvanur Dervisoglu ,
  • Mehmet Haklidir ,
  • Sule Caglayan ,
  • Lukasz Kurgan,
  • Vladimir Uversky,
  • Orkun Hasekioglu ,
  • Orkid Coskuner-Weber
Ibrahim Akbayrak
Turkish-German University

Corresponding Author:[email protected]

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Burak Ulver
TUBITAK Informatics and Information Security Research Center
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Havvanur Dervisoglu
TUBITAK Informatics and Information Security Research Center
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Mehmet Haklidir
TUBITAK Informatics and Information Security Research Center
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Sule Caglayan
Turkish-German University Faculty of Science
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Lukasz Kurgan
Virginia Commonwealth University
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Vladimir Uversky
University of South Florida
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Orkun Hasekioglu
TUBITAK Informatics and Information Security Research Center
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Orkid Coskuner-Weber
Turkish-German University Faculty of Science
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Abstract

A novel virus, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) worldwide appeared in 2019. Currently, we do not have a medicament that treats the disease. One of the rea-sons for the absence of treatment is related to the scarcity of detailed scientific knowledge of the members of the Coro-naviridae family, including the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Structural studies of the MERS-CoV proteins in the current literature are extremely limited. We present here detailed characterization of the struc-tural properties of MERS-CoV macro domain in aqueous solution at the atomic level with dynamics. For this study, we conducted extensive replica exchange molecular dynamics simulations linked to a generative neural networks and we use the resulting trajectories for structural analysis. We perform structural clustering based on the radius of gyration and end-to-end distance of MERS-CoV macro domain in aqueous solution with dynamics at the atomic level. We also report and analyze the residue-level intrinsic disorder features, flexibility and secondary structure. Furthermore, we study the pro-pensities of this macro domain for protein-protein interactions and for the RNA and DNA binding. Results are in agree-ment with available nuclear magnetic resonance spectroscopy findings and present more detailed insights into the struc-tural properties of MERS CoV macro domain. Overall, this work further shows that neural networks can be used as an exploratory tool for the studies of CoV family molecular conformational space at the nano level.
27 Jul 2020Submitted to PROTEINS: Structure, Function, and Bioinformatics
03 Aug 2020Submission Checks Completed
03 Aug 2020Assigned to Editor
03 Oct 2020Reviewer(s) Assigned
08 Nov 2020Review(s) Completed, Editorial Evaluation Pending
12 Dec 2020Editorial Decision: Revise Major
06 Feb 20211st Revision Received
13 Feb 2021Assigned to Editor
13 Feb 2021Submission Checks Completed
04 Mar 2021Reviewer(s) Assigned
14 Mar 2021Review(s) Completed, Editorial Evaluation Pending
17 Mar 2021Editorial Decision: Revise Minor
08 Apr 20212nd Revision Received
08 Apr 2021Assigned to Editor
08 Apr 2021Submission Checks Completed
03 May 2021Review(s) Completed, Editorial Evaluation Pending
03 May 2021Editorial Decision: Accept