Molecular Interactions of Polyphenolic Compounds Binding on Antiapoptotic Wild-Type and Mutated Bcl-2 Proteins

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Published: Sep 25, 2024
Keywords:
BH3-mimetics Computer-aided drug design Conformational dynamics Molecular docking Molecular dynamics simulations

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Ayomi Vidana Pathiranage
School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12120, Thailand
Kulpavee Jitapunkul
Department of Chemical Engineering, Faculty of Engineering, Kasetsart University, Bangkok 10900, Thailand
Anotai Suksangpanomrung
Department of Mechanical Engineering, Academic Division, Chulachomklao Royal Military Academy, Nakhon Nayok 26001, Thailand
Pisanu Toochinda
School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12120, Thailand
Luckhana Lawtrakul
School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12120, Thailand

Abstract

The molecular docking approach was used to determine the binding affinities and the interactions of B-cell lymphoma 2 (Bcl-2) both of wild-type and mutated Bcl-2 (Gly101Val) in complex with five polyphenolic compounds which were reported to have biological activity
in cancer therapy: Hesperetin, Quercetin, Cleomiscosin B, 5'-Methoxy-7'-epi-jatrorin A, and Procyanidin B2. The compounds were found to act as BH3-mimetics. They bind into the hydrophobic groove of BH3 motifs. Procyanidin B2 exhibited favorable binding free energies for both wild-type and mutated Bcl-2 (-8.30 to -8.80 kcal/mol). Molecular dynamics simulations and conformational analysis investigated the dynamics of Procyanidin B2 when bound to Bcl-2 in solution. Procyanidin B2 tightly binds to the hydrophobic groove of wildtype Bcl-2 (-24.79 kcal/mol) compared to the mutated species (-17.15 kcal/mol). Mutated residue in BH3 motifs induced structural changes, widening the hydrophobic cavity. This change potentially allows interference by surrounding water molecules, thereby weakening the protein-ligand interaction.

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How to Cite
Pathiranage , A. V. ., Jitapunkul , K., Suksangpanomrung , A., Toochinda , P., & Lawtrakul, L. (2024). Molecular Interactions of Polyphenolic Compounds Binding on Antiapoptotic Wild-Type and Mutated Bcl-2 Proteins. Science & Technology Asia, 29(3), 135–145. Retrieved from https://ph02.tci-thaijo.org/index.php/SciTechAsia/article/view/251986
Issue
Vol.29 No.3 (July-September 2024)
Section
Engineering
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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