research-article

In Silico Structure Based Designing of Dihydrofolate Reductase Enzyme Antagonists and Potential Small Molecules That Target DHFR Protein to Inhibit the Folic Acid Biosynthetic Pathways

Authors:

Mohammad Kawsar Sharif Siam,

Muhammad Sameer Hossain,

Eva Rahman Kabir,

Samiul Alam RajibAuthors Info & Claims

CSBio '17: Proceedings of the 8th International Conference on Computational Systems-Biology and Bioinformatics

Pages 62 - 67

https://doi.org/10.1145/3156346.3156358

Published: 07 December 2017 Publication History

Abstract

Cancer has several pathways by which it is developed in our body. Among them folic acid biosynthetic pathway is one where dihydrofolate reductase (DHFR) enzyme converts dihydrofolate into tetrahydrofolate which leads to unwanted and uncontrollable growth of tissues. Our aim of this study is to design DHFR antagonistic potential small molecules that inhibits Folic Acid Biosynthetic Pathways. In this study, Human DHFR obtained from Protein Data Bank (PDB) docked with several established anticancer drugs including Afatinib, Doxorubicin, Trimetrexate, Curcumin & Trimethoprim and several potential small molecules including Acarbose, Adenosine monophosphate, Abacavir, Aceprometazine & Isoxyl; obtained from PubChem and Drug Bank respectively. PyMOL and PyRx were used to visualize, curate and dock. For validation purpose Discovery Studio and Ramachandran Plot were run. Results after docking showed best binding affinities of established anticancer drugs with Human DHFR throughout the generations for example Methotrexate to Trimethoprim. Potential small molecules which belong from different therapeutic classes.

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Digital Library

Cited By

Sharif Siam MKarim ASharif Shohan M(2020)In-Silico Study for Potential Inhibitors of Both HSP72 and HSC70 Proteins in the Treatment of CancerCSBio '20: Proceedings of the Eleventh International Conference on Computational Systems-Biology and Bioinformatics10.1145/3429210.3429226(61-67)Online publication date: 19-Nov-2020
https://dl.acm.org/doi/10.1145/3429210.3429226
Sharif Siam MSarker ASayeem M(2020) In silico drug design and molecular docking studies targeting Akt1 (RAC-alpha serine/threonine-protein kinase) and Akt2 (RAC-beta serine/threonine-protein kinase) proteins and investigation of CYP (cytochrome P450) inhibitors against MAOB (monoamine oxidase B) for OSCC (oral squamous cell carcinoma) treatment Journal of Biomolecular Structure and Dynamics10.1080/07391102.2020.1802335(1-13)Online publication date: 4-Aug-2020
https://doi.org/10.1080/07391102.2020.1802335
Rajib SSharif Siam M(2019)Characterization and Analysis of Mammalian AKR7A Gene Promoters: Implications for Transcriptional RegulationBiochemical Genetics10.1007/s10528-019-09936-yOnline publication date: 16-Sep-2019
https://doi.org/10.1007/s10528-019-09936-y
Show More Cited By

Index Terms

In Silico Structure Based Designing of Dihydrofolate Reductase Enzyme Antagonists and Potential Small Molecules That Target DHFR Protein to Inhibit the Folic Acid Biosynthetic Pathways
1. Applied computing
  1. Life and medical sciences
    1. Computational biology
      1. Molecular structural biology
2. Computing methodologies
  1. Modeling and simulation
    1. Model development and analysis
      1. Modeling methodologies

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CSBio '17: Proceedings of the 8th International Conference on Computational Systems-Biology and Bioinformatics

December 2017

83 pages

ISBN:9781450353502

DOI:10.1145/3156346

Copyright © 2017 ACM.

Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

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SOICT: School of Information and Communication Technology - HUST
NAFOSTED: The National Foundation for Science and Technology Development
KMUTT: King Mongkut's University of Technology Thonburi

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Association for Computing Machinery

New York, NY, United States

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Published: 07 December 2017

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CSBio '17

CSBio '17: 8th International Conference on Computational Systems-Biology and Bioinformatics

December 7 - 8, 2017

Nha Trang City, Viet Nam

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Overall Acceptance Rate 23 of 37 submissions, 62%

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Cited By

Sharif Siam MKarim ASharif Shohan M(2020)In-Silico Study for Potential Inhibitors of Both HSP72 and HSC70 Proteins in the Treatment of CancerCSBio '20: Proceedings of the Eleventh International Conference on Computational Systems-Biology and Bioinformatics10.1145/3429210.3429226(61-67)Online publication date: 19-Nov-2020
https://dl.acm.org/doi/10.1145/3429210.3429226
Sharif Siam MSarker ASayeem M(2020) In silico drug design and molecular docking studies targeting Akt1 (RAC-alpha serine/threonine-protein kinase) and Akt2 (RAC-beta serine/threonine-protein kinase) proteins and investigation of CYP (cytochrome P450) inhibitors against MAOB (monoamine oxidase B) for OSCC (oral squamous cell carcinoma) treatment Journal of Biomolecular Structure and Dynamics10.1080/07391102.2020.1802335(1-13)Online publication date: 4-Aug-2020
https://doi.org/10.1080/07391102.2020.1802335
Rajib SSharif Siam M(2019)Characterization and Analysis of Mammalian AKR7A Gene Promoters: Implications for Transcriptional RegulationBiochemical Genetics10.1007/s10528-019-09936-yOnline publication date: 16-Sep-2019
https://doi.org/10.1007/s10528-019-09936-y
Siam MKabir EJurashe PShohan MRajib S(2018)Functional Analysis of iGlur Delta-2 and other Depression Associated ProteinsProceedings of the 9th International Conference on Computational Systems-Biology and Bioinformatics10.1145/3291757.3291765(1-10)Online publication date: 10-Dec-2018
https://dl.acm.org/doi/10.1145/3291757.3291765
Kabir ESiam MMustafa NKabir S(2018)Molecular Docking Reveals Pitavastatin and Related Molecules Antagonize 1DHF and Its Pseudogene DHFR2 in Cancer TreatmentProceedings of the 9th International Conference on Computational Systems-Biology and Bioinformatics10.1145/3291757.3291763(1-9)Online publication date: 10-Dec-2018
https://dl.acm.org/doi/10.1145/3291757.3291763

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