Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening

Lima Hazarika; Supriyo Sen; Jitesh Doshi

doi:doi:10.11648/j.cbb.20221002.11

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Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening

Lima Hazarika, Supriyo Sen, Jitesh Doshi

Published in Computational Biology and Bioinformatics (Volume 10, Issue 2)

Received: 17 July 2022 Accepted: 4 August 2022 Published: 17 August 2022

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Abstract

Apolipoprotein E (APOE) polymorphism is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The structural features of the isoforms (APOE2, APOE3, and APOE4) differ by only single amino acid that explicate their unique functions as lipid transporter with a role in cholesterol metabolism. It is therefore hypothesized that the cysteine/arginine change at position 112 results in structural differences within APOE3 and APOE4 leading to variation in binding affinities of ligands. We report for the first time computational and structural studies that reveal selectivity amongst ligands for APOE binding, with possible links to CAD pathogenesis. Molecular dynamics study allowed to understand the APOE conformational flexibility and its stability followed by Molecular docking studies that identified scaffold of Ligand 11802 by screening of 22,203 molecules from ChemDiv Library which showed the highest affinity towards APOE4. The ligand showed the presence of chemical moieties, similar to that present in known APOE4 stabilizers in Alzheimer’s Disease, which opened a possibility for the ligand as a potential therapeutic agent that could affect the behaviour of APOE4 in CAD pathogenesis. Further, ligand-binding preferences of each isoform with LDL receptors (LDLR) allowed understanding of the in-vivo mechanism in CAD pathogenesis.

Published in	Computational Biology and Bioinformatics (Volume 10, Issue 2)
DOI	10.11648/j.cbb.20221002.11
Page(s)	49-59
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

Cardiovascular, Apolipoprotein, Molecular Docking, SAR, Atherosclerosis

References

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APA Style

Lima Hazarika, Supriyo Sen, Jitesh Doshi. (2022). Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening. Computational Biology and Bioinformatics, 10(2), 49-59. https://doi.org/10.11648/j.cbb.20221002.11

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ACS Style

Lima Hazarika; Supriyo Sen; Jitesh Doshi. Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening. Comput. Biol. Bioinform. 2022, 10(2), 49-59. doi: 10.11648/j.cbb.20221002.11

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AMA Style

Lima Hazarika, Supriyo Sen, Jitesh Doshi. Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening. Comput Biol Bioinform. 2022;10(2):49-59. doi: 10.11648/j.cbb.20221002.11

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@article{10.11648/j.cbb.20221002.11,
  author = {Lima Hazarika and Supriyo Sen and Jitesh Doshi},
  title = {Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening},
  journal = {Computational Biology and Bioinformatics},
  volume = {10},
  number = {2},
  pages = {49-59},
  doi = {10.11648/j.cbb.20221002.11},
  url = {https://doi.org/10.11648/j.cbb.20221002.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cbb.20221002.11},
  abstract = {Apolipoprotein E (APOE) polymorphism is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The structural features of the isoforms (APOE2, APOE3, and APOE4) differ by only single amino acid that explicate their unique functions as lipid transporter with a role in cholesterol metabolism. It is therefore hypothesized that the cysteine/arginine change at position 112 results in structural differences within APOE3 and APOE4 leading to variation in binding affinities of ligands. We report for the first time computational and structural studies that reveal selectivity amongst ligands for APOE binding, with possible links to CAD pathogenesis. Molecular dynamics study allowed to understand the APOE conformational flexibility and its stability followed by Molecular docking studies that identified scaffold of Ligand 11802 by screening of 22,203 molecules from ChemDiv Library which showed the highest affinity towards APOE4. The ligand showed the presence of chemical moieties, similar to that present in known APOE4 stabilizers in Alzheimer’s Disease, which opened a possibility for the ligand as a potential therapeutic agent that could affect the behaviour of APOE4 in CAD pathogenesis. Further, ligand-binding preferences of each isoform with LDL receptors (LDLR) allowed understanding of the in-vivo mechanism in CAD pathogenesis.},
 year = {2022}
}

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TY  - JOUR
T1  - Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening
AU  - Lima Hazarika
AU  - Supriyo Sen
AU  - Jitesh Doshi
Y1  - 2022/08/17
PY  - 2022
N1  - https://doi.org/10.11648/j.cbb.20221002.11
DO  - 10.11648/j.cbb.20221002.11
T2  - Computational Biology and Bioinformatics
JF  - Computational Biology and Bioinformatics
JO  - Computational Biology and Bioinformatics
SP  - 49
EP  - 59
PB  - Science Publishing Group
SN  - 2330-8281
UR  - https://doi.org/10.11648/j.cbb.20221002.11
AB  - Apolipoprotein E (APOE) polymorphism is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The structural features of the isoforms (APOE2, APOE3, and APOE4) differ by only single amino acid that explicate their unique functions as lipid transporter with a role in cholesterol metabolism. It is therefore hypothesized that the cysteine/arginine change at position 112 results in structural differences within APOE3 and APOE4 leading to variation in binding affinities of ligands. We report for the first time computational and structural studies that reveal selectivity amongst ligands for APOE binding, with possible links to CAD pathogenesis. Molecular dynamics study allowed to understand the APOE conformational flexibility and its stability followed by Molecular docking studies that identified scaffold of Ligand 11802 by screening of 22,203 molecules from ChemDiv Library which showed the highest affinity towards APOE4. The ligand showed the presence of chemical moieties, similar to that present in known APOE4 stabilizers in Alzheimer’s Disease, which opened a possibility for the ligand as a potential therapeutic agent that could affect the behaviour of APOE4 in CAD pathogenesis. Further, ligand-binding preferences of each isoform with LDL receptors (LDLR) allowed understanding of the in-vivo mechanism in CAD pathogenesis.
VL  - 10
IS  - 2
ER  -

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Author Information

Lima Hazarika

Department of Biosciences, School of Life Sciences, Assam Don Bosco University, Guwahati, India
Supriyo Sen

Department of Biosciences, School of Life Sciences, Assam Don Bosco University, Guwahati, India
Jitesh Doshi

BioInsight Solutions (OPC) Private Limited, Navi Mumbai, India

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Plain Text BibTeX RIS

APA Style

Lima Hazarika, Supriyo Sen, Jitesh Doshi. (2022). Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening. Computational Biology and Bioinformatics, 10(2), 49-59. https://doi.org/10.11648/j.cbb.20221002.11

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ACS Style

Lima Hazarika; Supriyo Sen; Jitesh Doshi. Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening. Comput. Biol. Bioinform. 2022, 10(2), 49-59. doi: 10.11648/j.cbb.20221002.11

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AMA Style

Lima Hazarika, Supriyo Sen, Jitesh Doshi. Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening. Comput Biol Bioinform. 2022;10(2):49-59. doi: 10.11648/j.cbb.20221002.11

Copy | Download

@article{10.11648/j.cbb.20221002.11,
  author = {Lima Hazarika and Supriyo Sen and Jitesh Doshi},
  title = {Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening},
  journal = {Computational Biology and Bioinformatics},
  volume = {10},
  number = {2},
  pages = {49-59},
  doi = {10.11648/j.cbb.20221002.11},
  url = {https://doi.org/10.11648/j.cbb.20221002.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cbb.20221002.11},
  abstract = {Apolipoprotein E (APOE) polymorphism is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The structural features of the isoforms (APOE2, APOE3, and APOE4) differ by only single amino acid that explicate their unique functions as lipid transporter with a role in cholesterol metabolism. It is therefore hypothesized that the cysteine/arginine change at position 112 results in structural differences within APOE3 and APOE4 leading to variation in binding affinities of ligands. We report for the first time computational and structural studies that reveal selectivity amongst ligands for APOE binding, with possible links to CAD pathogenesis. Molecular dynamics study allowed to understand the APOE conformational flexibility and its stability followed by Molecular docking studies that identified scaffold of Ligand 11802 by screening of 22,203 molecules from ChemDiv Library which showed the highest affinity towards APOE4. The ligand showed the presence of chemical moieties, similar to that present in known APOE4 stabilizers in Alzheimer’s Disease, which opened a possibility for the ligand as a potential therapeutic agent that could affect the behaviour of APOE4 in CAD pathogenesis. Further, ligand-binding preferences of each isoform with LDL receptors (LDLR) allowed understanding of the in-vivo mechanism in CAD pathogenesis.},
 year = {2022}
}

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TY  - JOUR
T1  - Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening
AU  - Lima Hazarika
AU  - Supriyo Sen
AU  - Jitesh Doshi
Y1  - 2022/08/17
PY  - 2022
N1  - https://doi.org/10.11648/j.cbb.20221002.11
DO  - 10.11648/j.cbb.20221002.11
T2  - Computational Biology and Bioinformatics
JF  - Computational Biology and Bioinformatics
JO  - Computational Biology and Bioinformatics
SP  - 49
EP  - 59
PB  - Science Publishing Group
SN  - 2330-8281
UR  - https://doi.org/10.11648/j.cbb.20221002.11
AB  - Apolipoprotein E (APOE) polymorphism is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The structural features of the isoforms (APOE2, APOE3, and APOE4) differ by only single amino acid that explicate their unique functions as lipid transporter with a role in cholesterol metabolism. It is therefore hypothesized that the cysteine/arginine change at position 112 results in structural differences within APOE3 and APOE4 leading to variation in binding affinities of ligands. We report for the first time computational and structural studies that reveal selectivity amongst ligands for APOE binding, with possible links to CAD pathogenesis. Molecular dynamics study allowed to understand the APOE conformational flexibility and its stability followed by Molecular docking studies that identified scaffold of Ligand 11802 by screening of 22,203 molecules from ChemDiv Library which showed the highest affinity towards APOE4. The ligand showed the presence of chemical moieties, similar to that present in known APOE4 stabilizers in Alzheimer’s Disease, which opened a possibility for the ligand as a potential therapeutic agent that could affect the behaviour of APOE4 in CAD pathogenesis. Further, ligand-binding preferences of each isoform with LDL receptors (LDLR) allowed understanding of the in-vivo mechanism in CAD pathogenesis.
VL  - 10
IS  - 2
ER  -

Copy | Download