Elucidating the Interaction of Squamostatin A and Xylomaticin with Bcl-xl Protein: A Molecular Docking and Dynamics Study in Ovarian Cancer
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Abstract
Introduction: The B-cell lymphoma-extra-large (Bcl-xL) protein has emerged as an essential target in cancer therapeutics due to its pivotal role in regulating apoptosis and cell survival. Bcl-xL protein has been found to be overexpressed and associated to ovarian cancer. It has been targeted by various ligands, including both synthetic and natural compounds. Materials and methods: Molecular docking was performed by AutoDock Vina software. The MD simulation for the complexes were conducted using the AMBER 2022.1 package. Results: Molecular docking analysis revealed that both squamostatin A and xylomaticin possess good binding affinities of –10.9 kcal/mol and –11.6 kcal/mol, respectively. Detailed analysis of the binding modes showed hydrogen bonds and hydrophobic contacts emphasise the stability of the squamostatin A/Bcl-xL and xylomaticin/Bcl-xL complexes. Our findings on molecular dynamics provided both complexes maintained stable over 100 ns within the Bcl-xL protein with RMSD average value of 1.53 ± 0.20 Å (squamostatin A) and 1.13 ± 0.12 Å (xylomaticin). Conclusion: Computational investigation underlines the potential of squamostatin A and xylomaticin as promising candidates for Bcl-xL-targeted therapies. The good and stable binding interaction were observed, incorporated with their structural stability during molecular dynamics simulations, demand further experimental validation to come up with valuable insights for new drug discovery, particularly in cancer therapeutics.
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