Journal of pharmacy & bioallied sciences · 2025
Molecular Docking and Dynamics Simulation Reveal Stable Binding of Tiliroside in the Colchicine Site of Tubulin.
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Asfour Hani Z, Mohamed Hagar M, Omar Abdelsattar M, Alhakamy Nabil A, Mohamed Gamal A, El-Agamy Dina S, Ibrahim Sabrin R M
Аннотация
BACKGROUND: The colchicine-binding site on tubulin is of particular interest for new drug development due to its role in microtubule destabilization and potential to overcome resistance to other agents. Tiliroside, a naturally occurring flavonoid glycoside, has demonstrated anticancer potential in vitro, but its interaction with tubulin has not been previously elucidated.
OBJECTIVE: This study aimed to investigate the binding of tiliroside to the tubulin site of colchicine, in comparison with colchicine.
METHODS: Molecular docking and molecular dynamics (MD) simulations were employed. Induced-fit docking predicted tiliroside binding, and redocking of colchicine was used to validate the docking protocol. MD simulations (100 ns) were conducted for both tubulin-tiliroside and tubulin-colchicine complexes.
RESULTS: Induced-fit docking predicted that tiliroside binds strongly in the colchicine site, with more favorable scoring metrics than colchicine (Glide GScore -16.77 vs -10.25, and MMGBSA ΔGbind -50.46 vs -36.62 kcal/mol). Redocking of colchicine reproduced the binding pose (root-mean-square deviation (RMSD) ~0.6 Å). MD simulations further revealed that tiliroside forms a stable complex, remaining securely bound in the pocket. Tiliroside maintained multiple hydrogen bonds and hydrophobic contacts with tubulin, similar to or more persistent than those of colchicine.
CONCLUSION: These results suggest that tiliroside can stably and snugly occupy the colchicine site of tubulin. In summary, our computational study provides structural and dynamic evidence that tiliroside is a high-affinity ligand for the colchicine site, supporting its potential as a lead compound for developing new tubulin-targeted anticancer agents.
OBJECTIVE: This study aimed to investigate the binding of tiliroside to the tubulin site of colchicine, in comparison with colchicine.
METHODS: Molecular docking and molecular dynamics (MD) simulations were employed. Induced-fit docking predicted tiliroside binding, and redocking of colchicine was used to validate the docking protocol. MD simulations (100 ns) were conducted for both tubulin-tiliroside and tubulin-colchicine complexes.
RESULTS: Induced-fit docking predicted that tiliroside binds strongly in the colchicine site, with more favorable scoring metrics than colchicine (Glide GScore -16.77 vs -10.25, and MMGBSA ΔGbind -50.46 vs -36.62 kcal/mol). Redocking of colchicine reproduced the binding pose (root-mean-square deviation (RMSD) ~0.6 Å). MD simulations further revealed that tiliroside forms a stable complex, remaining securely bound in the pocket. Tiliroside maintained multiple hydrogen bonds and hydrophobic contacts with tubulin, similar to or more persistent than those of colchicine.
CONCLUSION: These results suggest that tiliroside can stably and snugly occupy the colchicine site of tubulin. In summary, our computational study provides structural and dynamic evidence that tiliroside is a high-affinity ligand for the colchicine site, supporting its potential as a lead compound for developing new tubulin-targeted anticancer agents.