Study of the antidiabetic mechanism of berberine compound on FOXO1 transcription factor through molecular docking and molecular dynamics simulations,Journal of Molecular Modeling

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Study of the antidiabetic mechanism of berberine compound on FOXO1 transcription factor through molecular docking and molecular dynamics simulations
Journal of Molecular Modeling ( IF 2.1 ) Pub Date : 2024-07-09 , DOI: 10.1007/s00894-024-06060-6
Iman Permana Maksum ₁ , Rustaman Rustaman ₁ , Yusi Deawati ₁ , Yaya Rukayadi ₂ , Ayudiah Rizki Utami ₁ , Zahra Khira Nafisa ₃

Affiliation

Context

Diabetes mellitus (DM) is a metabolic disorder disease that causes hyperglycemia conditions and associated with various chronic complications leading to mortality. Due to high toxicity of conventional diabetic drugs, the exploration of natural compounds as alternative diabetes treatments has been widely carried out. Previous in silico studies have highlighted berberine, a natural compound, as a promising alternative in antidiabetic therapy, potentially acting through various pathways, including the inhibition of the FOXO1 transcription factor in the gluconeogenesis pathway. However, the specific mechanism by which berberine interacts with FOXO1 remains unclear, and research in this area is relatively limited. Therefore, this study aims to determine the stability of berberine structure with FOXO1 based on RMSD, RMSF, binding energy, and trajectory analysis to determine the potential of berberine to inhibit the gluconeogenesis pathway. This research was conducted by in silico method with molecular docking using AutoDock4.2 and molecular dynamics study using Amber20, then visualized by VMD.

Methods

Docking between ligand and FOXO1 receptor was carried out with Autodock4.2. For molecular dynamics simulations, the force fields of DNA.OL15, protein.ff14SB, gaff2, and tip3p were used.

中文翻译：

通过分子对接和分子动力学模拟研究小檗碱化合物对FOXO1转录因子的抗糖尿病机制

语境

糖尿病 (DM) 是一种代谢紊乱性疾病，会导致高血糖并与各种导致死亡的慢性并发症相关。由于常规糖尿病药物毒性较高，天然化合物作为糖尿病替代治疗的探索已广泛开展。先前的计算机研究强调小檗碱（一种天然化合物）是抗糖尿病治疗中一种有前景的替代品，可能通过多种途径发挥作用，包括抑制糖异生途径中的 FOXO1 转录因子。然而，小檗碱与FOXO1相互作用的具体机制仍不清楚，这方面的研究也相对有限。因此，本研究旨在基于RMSD、RMSF、结合能和轨迹分析确定小檗碱结构与FOXO1的稳定性，以确定小檗碱抑制糖异生途径的潜力。这项研究是通过计算机方法进行的，使用 AutoDock4.2 进行分子对接，并使用 Amber20 进行分子动力学研究，然后通过 VMD 进行可视化。