Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists

Purpose: To identify the structural requirements for designing a lead key for insulin-like growth factor (IGF-1R) inhibition using group-based quantitative structure activity relationship (GQSAR) and molecular docking. Methods: GQSAR method requires fragmentation of molecules. The molecules in the...

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Main Authors:	Abdullahi, Abubakar Danjuma, Abdualkader, Abdualrahman Mohammed, Abdulsamat, Nadiahanis, Ingale, Kundan
Format:	Article
Language:	English English
Published:	Pharmacotherapy Group 2015
Subjects:	QD Chemistry RS Pharmacy and materia medica
Online Access:	http://irep.iium.edu.my/49051/ http://irep.iium.edu.my/49051/ http://irep.iium.edu.my/49051/ http://irep.iium.edu.my/49051/1/Application_of_Group-Based_QSAR_and_Molecular_Docking_in_the_Design_of_Insulin-Like_Growth_Factor_Antagonists.pdf http://irep.iium.edu.my/49051/4/49051_Application%20of%20group-based%20QSAR%20and%20molecular_SCOPUS.pdf

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spelling	iium-490512017-12-14T03:18:58Z http://irep.iium.edu.my/49051/ Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists Abdullahi, Abubakar Danjuma Abdualkader, Abdualrahman Mohammed Abdulsamat, Nadiahanis Ingale, Kundan QD Chemistry RS Pharmacy and materia medica Purpose: To identify the structural requirements for designing a lead key for insulin-like growth factor (IGF-1R) inhibition using group-based quantitative structure activity relationship (GQSAR) and molecular docking. Methods: GQSAR method requires fragmentation of molecules. The molecules in the current dataset were fragmented into three (R1, R2 and R3) by applying common fragmentation pattern, and fragment- based 2D descriptors were then calculated. GQSAR models were derived by applying various methods including multiple linear regressions and partial least square or k-nearest neighbour. Results: Four generated GQSAR models were selected based on the statistical significance of the model. It was found that the presence of flexible and non-aromatic groups on fragment R1 was conducive for inhibition. Additionally, the existence of amino groups as hydrogen bond donors at fragments R2 and R3 was fruitful for inhibition. Docking studies revealed the binding orientation adopted by the active compounds at several amino acid residues, including Met 1126, Arg, 1128, Met 1052, GLU 1050, Met 1112, Leu 1051, Met 1049, Val 1033, and Val 983 at ATP binding sites of IGF-1R kinase domain. Conclusion: The generated models provide a site-specific insight into the structural requirements for IGF-1R inhibition which can be used to design and develop potent inhibitors. Keywords: Insulin-like growth factor 1 (IGF-1) receptor, Quantitative structure-activity relationship, Adenosine triphosphate, Competitive inhibitors, Electrotopological state index. Pharmacotherapy Group 2015-06-14 Article PeerReviewed application/pdf en http://irep.iium.edu.my/49051/1/Application_of_Group-Based_QSAR_and_Molecular_Docking_in_the_Design_of_Insulin-Like_Growth_Factor_Antagonists.pdf application/pdf en http://irep.iium.edu.my/49051/4/49051_Application%20of%20group-based%20QSAR%20and%20molecular_SCOPUS.pdf Abdullahi, Abubakar Danjuma and Abdualkader, Abdualrahman Mohammed and Abdulsamat, Nadiahanis and Ingale, Kundan (2015) Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists. Tropical Journal of Pharmadeutical Research, 14 (6). pp. 942-951. ISSN 1596-5996 E-ISSN 1596-9827 http://www.tjpr.org 003
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English
topic	QD Chemistry RS Pharmacy and materia medica
spellingShingle	QD Chemistry RS Pharmacy and materia medica Abdullahi, Abubakar Danjuma Abdualkader, Abdualrahman Mohammed Abdulsamat, Nadiahanis Ingale, Kundan Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists
description	Purpose: To identify the structural requirements for designing a lead key for insulin-like growth factor (IGF-1R) inhibition using group-based quantitative structure activity relationship (GQSAR) and molecular docking. Methods: GQSAR method requires fragmentation of molecules. The molecules in the current dataset were fragmented into three (R1, R2 and R3) by applying common fragmentation pattern, and fragment- based 2D descriptors were then calculated. GQSAR models were derived by applying various methods including multiple linear regressions and partial least square or k-nearest neighbour. Results: Four generated GQSAR models were selected based on the statistical significance of the model. It was found that the presence of flexible and non-aromatic groups on fragment R1 was conducive for inhibition. Additionally, the existence of amino groups as hydrogen bond donors at fragments R2 and R3 was fruitful for inhibition. Docking studies revealed the binding orientation adopted by the active compounds at several amino acid residues, including Met 1126, Arg, 1128, Met 1052, GLU 1050, Met 1112, Leu 1051, Met 1049, Val 1033, and Val 983 at ATP binding sites of IGF-1R kinase domain. Conclusion: The generated models provide a site-specific insight into the structural requirements for IGF-1R inhibition which can be used to design and develop potent inhibitors. Keywords: Insulin-like growth factor 1 (IGF-1) receptor, Quantitative structure-activity relationship, Adenosine triphosphate, Competitive inhibitors, Electrotopological state index.
format	Article
author	Abdullahi, Abubakar Danjuma Abdualkader, Abdualrahman Mohammed Abdulsamat, Nadiahanis Ingale, Kundan
author_facet	Abdullahi, Abubakar Danjuma Abdualkader, Abdualrahman Mohammed Abdulsamat, Nadiahanis Ingale, Kundan
author_sort	Abdullahi, Abubakar Danjuma
title	Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists
title_short	Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists
title_full	Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists
title_fullStr	Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists
title_full_unstemmed	Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists
title_sort	application of group-based qsar and molecular docking in the design of insulin-like growth factor antagonists
publisher	Pharmacotherapy Group
publishDate	2015
url	http://irep.iium.edu.my/49051/ http://irep.iium.edu.my/49051/ http://irep.iium.edu.my/49051/ http://irep.iium.edu.my/49051/1/Application_of_Group-Based_QSAR_and_Molecular_Docking_in_the_Design_of_Insulin-Like_Growth_Factor_Antagonists.pdf http://irep.iium.edu.my/49051/4/49051_Application%20of%20group-based%20QSAR%20and%20molecular_SCOPUS.pdf
first_indexed	2023-09-18T21:09:24Z
last_indexed	2023-09-18T21:09:24Z
_version_	1777411150943617024

Application of group-based QSAR and molecular docking in the design of insulin-like growth factor antagonists

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