3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors

PGAM1 is overexpressed in a wide range of cancers, thereby promoting cancer cell proliferation and tumor growth, so it is gradually becoming an attractive target. Recently, a series of inhibitors with various structures targeting PGAM1 have been reported, particularly anthraquinone derivatives. In p...

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Autores principales:	Yuwei Wang, Yifan Guo, Shaojia Qiang, Ruyi Jin, Zhi Li, Yuping Tang, Elaine Lai Han Leung, Hui Guo, Xiaojun Yao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	PGAM1 molecular docking molecular dynamics simulation CoMFA CoMSIA Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/8cec5f56ef37483e819724364358a0e2
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spelling	oai:doaj.org-article:8cec5f56ef37483e819724364358a0e22021-12-01T01:32:50Z3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors1663-981210.3389/fphar.2021.764351https://doaj.org/article/8cec5f56ef37483e819724364358a0e22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.764351/fullhttps://doaj.org/toc/1663-9812PGAM1 is overexpressed in a wide range of cancers, thereby promoting cancer cell proliferation and tumor growth, so it is gradually becoming an attractive target. Recently, a series of inhibitors with various structures targeting PGAM1 have been reported, particularly anthraquinone derivatives. In present study, the structure–activity relationships and binding mode of a series of anthraquinone derivatives were probed using three-dimensional quantitative structure–activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, r2 = 0.97, q2 = 0.81) and comparative molecular similarity indices analysis (CoMSIA, r2 = 0.96, q2 = 0.82) techniques were performed to produce 3D-QSAR models, which demonstrated satisfactory results, especially for the good predictive abilities. In addition, molecular dynamics (MD) simulations technology was employed to understand the key residues and the dominated interaction between PGAM1 and inhibitors. The decomposition of binding free energy indicated that the residues of F22, K100, V112, W115, and R116 play a vital role during the ligand binding process. The hydrogen bond analysis showed that R90, W115, and R116 form stable hydrogen bonds with PGAM1 inhibitors. Based on the above results, 7 anthraquinone compounds were designed and exhibited the expected predictive activity. The study explored the structure–activity relationships of anthraquinone compounds through 3D-QSAR and molecular dynamics simulations and provided theoretical guidance for the rational design of new anthraquinone derivatives as PGAM1 inhibitors.Yuwei WangYifan GuoShaojia QiangRuyi JinZhi LiYuping TangElaine Lai Han LeungElaine Lai Han LeungHui GuoXiaojun YaoXiaojun YaoFrontiers Media S.A.articlePGAM1molecular dockingmolecular dynamics simulationCoMFACoMSIATherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PGAM1 molecular docking molecular dynamics simulation CoMFA CoMSIA Therapeutics. Pharmacology RM1-950
spellingShingle	PGAM1 molecular docking molecular dynamics simulation CoMFA CoMSIA Therapeutics. Pharmacology RM1-950 Yuwei Wang Yifan Guo Shaojia Qiang Ruyi Jin Zhi Li Yuping Tang Elaine Lai Han Leung Elaine Lai Han Leung Hui Guo Xiaojun Yao Xiaojun Yao 3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors
description	PGAM1 is overexpressed in a wide range of cancers, thereby promoting cancer cell proliferation and tumor growth, so it is gradually becoming an attractive target. Recently, a series of inhibitors with various structures targeting PGAM1 have been reported, particularly anthraquinone derivatives. In present study, the structure–activity relationships and binding mode of a series of anthraquinone derivatives were probed using three-dimensional quantitative structure–activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, r2 = 0.97, q2 = 0.81) and comparative molecular similarity indices analysis (CoMSIA, r2 = 0.96, q2 = 0.82) techniques were performed to produce 3D-QSAR models, which demonstrated satisfactory results, especially for the good predictive abilities. In addition, molecular dynamics (MD) simulations technology was employed to understand the key residues and the dominated interaction between PGAM1 and inhibitors. The decomposition of binding free energy indicated that the residues of F22, K100, V112, W115, and R116 play a vital role during the ligand binding process. The hydrogen bond analysis showed that R90, W115, and R116 form stable hydrogen bonds with PGAM1 inhibitors. Based on the above results, 7 anthraquinone compounds were designed and exhibited the expected predictive activity. The study explored the structure–activity relationships of anthraquinone compounds through 3D-QSAR and molecular dynamics simulations and provided theoretical guidance for the rational design of new anthraquinone derivatives as PGAM1 inhibitors.
format	article
author	Yuwei Wang Yifan Guo Shaojia Qiang Ruyi Jin Zhi Li Yuping Tang Elaine Lai Han Leung Elaine Lai Han Leung Hui Guo Xiaojun Yao Xiaojun Yao
author_facet	Yuwei Wang Yifan Guo Shaojia Qiang Ruyi Jin Zhi Li Yuping Tang Elaine Lai Han Leung Elaine Lai Han Leung Hui Guo Xiaojun Yao Xiaojun Yao
author_sort	Yuwei Wang
title	3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors
title_short	3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors
title_full	3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors
title_fullStr	3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors
title_full_unstemmed	3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors
title_sort	3d-qsar, molecular docking, and md simulations of anthraquinone derivatives as pgam1 inhibitors
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/8cec5f56ef37483e819724364358a0e2
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3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors

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