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

Shiliang Wu

doi:doi:10.11648/j.abb.20210901.13

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

Shiliang Wu

Published in Advances in Bioscience and Bioengineering (Volume 9, Issue 1)

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), 2024. Published by Science Publishing Group

Keywords

Molecular Dynamics Simulations, Principal Component Analysis, MM-GBSA

References

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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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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
SP  - 13
EP  - 19
PB  - Science Publishing Group
SN  - 2330-4162
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

Shiliang Wu

School of Science, Shandong Jiaotong University, Jinan, China

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Plain Text BibTeX RIS

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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

Copy | Download

@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}
}

Copy | Download

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
SP  - 13
EP  - 19
PB  - Science Publishing Group
SN  - 2330-4162
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  -

Copy | Download