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Roles of Integration of Multiple Simulation Technologies in Insights into Binding Mechanism of Inhibitors to BRD Family

Received: 16 March 2021     Accepted: 30 March 2021     Published: 12 April 2021
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Abstract

Insights into binding mechanism of inhibitors to targets are expected to provide a meaningfully theoretical guidance for design and development of effective inhibitors inhibiting of the activity of targets. It is well known that the bromodomain (BRD) family has been thought as a promising target utilized for treating various human diseases, such as inflammatory disorders, malignant tumors, acute myelogenous leukemia (AML), bone diseases, etc. In this work, we summarize the roles of integration of multiple simulation technologies in exploring atomic-level dynamics changes of the BRD family because of inhibitor bindings. Molecular dynamics (MD) simulations, binding free energy calculations, calculations of dynamics cross-correlation maps (DCCMs), and principal component (PC) analysis are integrated together to uncover binding modes of inhibitors to BRDs. The results obtained from binding free energy calculations can measure binding ability of inhibitors to BRDs, and explore the main driving forces of the binding of inhibitors to BRDs. The information stemming from PC analysis can reveal the changes in conformations, internal dynamics and movement patterns of BRDs due to inhibitor associations. Residue-based free energy decomposition method is wielded to unveil contributions of separate residues to inhibitor bindings, and explore the decisive factors that affect the bindings of inhibitors to BRDs.

Published in Advances in Bioscience and Bioengineering (Volume 9, Issue 1)
DOI 10.11648/j.abb.20210901.13
Page(s) 13-19
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Molecular Dynamics Simulations, Principal Component Analysis, MM-GBSA

References
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  • APA Style

    Shiliang Wu. (2021). Roles of Integration of Multiple Simulation Technologies in Insights into Binding Mechanism of Inhibitors to BRD Family. Advances in Bioscience and Bioengineering, 9(1), 13-19. https://doi.org/10.11648/j.abb.20210901.13

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    ACS Style

    Shiliang Wu. Roles of Integration of Multiple Simulation Technologies in Insights into Binding Mechanism of Inhibitors to BRD Family. Adv. BioSci. Bioeng. 2021, 9(1), 13-19. doi: 10.11648/j.abb.20210901.13

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    AMA Style

    Shiliang Wu. Roles of Integration of Multiple Simulation Technologies in Insights into Binding Mechanism of Inhibitors to BRD Family. Adv BioSci Bioeng. 2021;9(1):13-19. doi: 10.11648/j.abb.20210901.13

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  • @article{10.11648/j.abb.20210901.13,
      author = {Shiliang Wu},
      title = {Roles of Integration of Multiple Simulation Technologies in Insights into Binding Mechanism of Inhibitors to BRD Family},
      journal = {Advances in Bioscience and Bioengineering},
      volume = {9},
      number = {1},
      pages = {13-19},
      doi = {10.11648/j.abb.20210901.13},
      url = {https://doi.org/10.11648/j.abb.20210901.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.abb.20210901.13},
      abstract = {Insights into binding mechanism of inhibitors to targets are expected to provide a meaningfully theoretical guidance for design and development of effective inhibitors inhibiting of the activity of targets. It is well known that the bromodomain (BRD) family has been thought as a promising target utilized for treating various human diseases, such as inflammatory disorders, malignant tumors, acute myelogenous leukemia (AML), bone diseases, etc. In this work, we summarize the roles of integration of multiple simulation technologies in exploring atomic-level dynamics changes of the BRD family because of inhibitor bindings. Molecular dynamics (MD) simulations, binding free energy calculations, calculations of dynamics cross-correlation maps (DCCMs), and principal component (PC) analysis are integrated together to uncover binding modes of inhibitors to BRDs. The results obtained from binding free energy calculations can measure binding ability of inhibitors to BRDs, and explore the main driving forces of the binding of inhibitors to BRDs. The information stemming from PC analysis can reveal the changes in conformations, internal dynamics and movement patterns of BRDs due to inhibitor associations. Residue-based free energy decomposition method is wielded to unveil contributions of separate residues to inhibitor bindings, and explore the decisive factors that affect the bindings of inhibitors to BRDs.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - Roles of Integration of Multiple Simulation Technologies in Insights into Binding Mechanism of Inhibitors to BRD Family
    AU  - Shiliang Wu
    Y1  - 2021/04/12
    PY  - 2021
    N1  - https://doi.org/10.11648/j.abb.20210901.13
    DO  - 10.11648/j.abb.20210901.13
    T2  - Advances in Bioscience and Bioengineering
    JF  - Advances in Bioscience and Bioengineering
    JO  - Advances in Bioscience and Bioengineering
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    PB  - Science Publishing Group
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    UR  - https://doi.org/10.11648/j.abb.20210901.13
    AB  - Insights into binding mechanism of inhibitors to targets are expected to provide a meaningfully theoretical guidance for design and development of effective inhibitors inhibiting of the activity of targets. It is well known that the bromodomain (BRD) family has been thought as a promising target utilized for treating various human diseases, such as inflammatory disorders, malignant tumors, acute myelogenous leukemia (AML), bone diseases, etc. In this work, we summarize the roles of integration of multiple simulation technologies in exploring atomic-level dynamics changes of the BRD family because of inhibitor bindings. Molecular dynamics (MD) simulations, binding free energy calculations, calculations of dynamics cross-correlation maps (DCCMs), and principal component (PC) analysis are integrated together to uncover binding modes of inhibitors to BRDs. The results obtained from binding free energy calculations can measure binding ability of inhibitors to BRDs, and explore the main driving forces of the binding of inhibitors to BRDs. The information stemming from PC analysis can reveal the changes in conformations, internal dynamics and movement patterns of BRDs due to inhibitor associations. Residue-based free energy decomposition method is wielded to unveil contributions of separate residues to inhibitor bindings, and explore the decisive factors that affect the bindings of inhibitors to BRDs.
    VL  - 9
    IS  - 1
    ER  - 

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Author Information
  • School of Science, Shandong Jiaotong University, Jinan, China

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