Integrative in silico analysis to explore the potential of Zingiberaceae compounds to inhibit estrogen receptor alpha activity in breast cancer

IF 2.7 4区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of molecular graphics & modelling Pub Date : 2025-03-18 DOI:10.1016/j.jmgm.2025.109023

Amit Dubey , Hamad A. Al-Lohedan , Mohd Sajid Ali , Andrea Ragusa

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Abstract

The estrogen receptor alpha (ERα) is a critical player in breast cancer progression, making it a key target for therapeutic development. This study employed an advanced computational method to discover potential inhibitors of ERα from a library of compounds from the Zingiberaceae family. The workflow includes virtual screening, re-docking, molecular dynamics (MD) simulations, radius of gyration (RG), and root mean-square deviation (RMSD)-based free energy landscape (FEL) analysis. This multifaceted strategy led to the selection of four compounds with superior docking scores compared to established control molecules. The MD simulation assessments confirmed that these selected compounds exhibited robust stability and favorable binding interactions within the ERα binding pocket. Notably, the pocket volume analysis of the minimum energy structures obtained from FEL analysis indicated a significant reduction in volume compared to the initial docking poses, suggesting a more compact and potentially more effective binding conformation. These findings highlight the potential of Zingiberaceae family-derived compounds as promising candidates for ERα inhibition. The stability of these interactions and the observed compactness of the binding pocket, as demonstrated by our comprehensive computational analysis, underscore the potential of these compounds for further preclinical evaluation.

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通过整合性硅学分析探索银杏科化合物抑制乳腺癌雌激素受体α活性的潜力

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来源期刊

Journal of molecular graphics & modelling 生物-计算机：跨学科应用

CiteScore

5.50

自引率

6.90%

发文量

216

审稿时长

35 days

期刊介绍： The Journal of Molecular Graphics and Modelling is devoted to the publication of papers on the uses of computers in theoretical investigations of molecular structure, function, interaction, and design. The scope of the journal includes all aspects of molecular modeling and computational chemistry, including, for instance, the study of molecular shape and properties, molecular simulations, protein and polymer engineering, drug design, materials design, structure-activity and structure-property relationships, database mining, and compound library design. As a primary research journal, JMGM seeks to bring new knowledge to the attention of our readers. As such, submissions to the journal need to not only report results, but must draw conclusions and explore implications of the work presented. Authors are strongly encouraged to bear this in mind when preparing manuscripts. Routine applications of standard modelling approaches, providing only very limited new scientific insight, will not meet our criteria for publication. Reproducibility of reported calculations is an important issue. Wherever possible, we urge authors to enhance their papers with Supplementary Data, for example, in QSAR studies machine-readable versions of molecular datasets or in the development of new force-field parameters versions of the topology and force field parameter files. Routine applications of existing methods that do not lead to genuinely new insight will not be considered.