RESUMO
Objective To study the interaction mechanism of anti-cancer drug docetaxel (DTX) andβ-tubulin, to determine the binding sites and the involved amino acids between the β-tubulin and docetaxel, and to analyze the dynamic combination process. Methods The docking binding energy and interaction sites of DTX molecules withβ-tubulin on the potential energy surface were calculated by molecular docking method. The dynamic interaction process of the low binding energy DTX with β-tubulin was simulated by molecular dynamics method. Results The results of molecular docking showed that there are three interaction sites, including N1, N2 and N3, between DTX and β-tubulin. The DTX molecules with structure of No.1, 2 and 4, which have excellent docking energy, were chose for molecular dynamics simulation. As a result, the dynamic change processes of the system complexes from non-equilibrium to equilibrium were obtained. The simulation results showed that the hydrogen bonds formed by the DTX with structure No.1 were significantly higher than those with structures No. 2 and 4. The solvent accessibility surface area of the DTX with structures No.1, 2 and 4 was higher than that of paclitaxel. Conclusion The model of DTX binding toβ-tubulin was established, which could provide theoretical guidance for the design and development of novel paclitaxel anticancer drugs.