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

• Published in: Journal of molecular modeling 2024-08, Vol.30 (8), p.260, Article 260
• Main Authors: Maksum, Iman Permana, Rustaman, Rustaman, Deawati, Yusi, Rukayadi, Yaya, Utami, Ayudiah Rizki, Nafisa, Zahra Khira
• Format: Article
• Language: English
• Subjects: Antidiabetics; Berberine - chemistry; Berberine - pharmacology; Binding Sites; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Diabetes; Diabetes mellitus; Dynamic structural analysis; Forkhead Box Protein O1 - chemistry; Forkhead Box Protein O1 - metabolism; Humans; Hyperglycemia; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Ligands; Metabolic disorders; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular Dynamics Simulation; Molecular Medicine; Molecular structure; Original Paper; Protein Binding; Theoretical and Computational Chemistry; Toxic diseases; Trajectory analysis; Transcription factors
• ISSN: 1610-2940; 0948-5023; 0948-5023
• DOI: 10.1007/s00894-024-06060-6

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.