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Molecular Interactionsof Polyphenolic Compounds Binding on Antiapoptotic Wild-Type and Mutated Bcl-2 Proteins |
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| รหัสดีโอไอ | |
| Creator | Luckhana Lawtrakul |
| Title | Molecular Interactionsof Polyphenolic Compounds Binding on Antiapoptotic Wild-Type and Mutated Bcl-2 Proteins |
| Contributor | Ayomi Vidana Pathiranage, Kulpavee Jitapunkul, Anotai Suksangpanomrung, Pisanu Toochinda |
| Publisher | Research Administration Division |
| Publication Year | 2567 |
| Journal Title | Science & Technology Asia |
| Journal Vol. | 29 |
| Journal No. | 3 |
| Page no. | 135-145 |
| Keyword | BH3-mimetics, Computer-aided drug design, Conformational dynamics, Molecular docking, Molecular dynamics simulations |
| URL Website | https://www.tci-thaijo.org/index.php/SciTechAsia/index |
| Website title | ThaiJo2 |
| ISSN | 2586-9000 |
| Abstract | The molecular docking approach was used to determine the binding affinities andthe interactions of B-cell lymphoma 2 (Bcl-2) both of wild-type andmutated Bcl-2 (Gly101Val) in complex with five polyphenolic compounds which were reported to have biological activityin 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 wild-typeBcl-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. |
