A preliminary study of binding site on β-tubulin interacting with the new anti-cancer drug docetaxel
10.3760/cma.j.issn.1673-4181.2017.06.004
- VernacularTitle:新型抗癌药物多西他赛与β-微管蛋白作用位点的初步研究
- Author:
Chuancai SUN
1
;
Chao ZHANG
;
Lijuan ZHU
;
Cuihong WANG
;
Meiling ZHANG
Author Information
1. 300070,天津医科大学生物医学工程与技术学院
- Keywords:
Docetaxel;
β-tubulin;
Structure optimization;
Active sites;
Dynamic simulation
- From:
International Journal of Biomedical Engineering
2017;40(6):421-425,431
- CountryChina
- Language:Chinese
-
Abstract:
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.
