By docking simulation, the binding modes of the colchicine-site inhibitors with β-tubulin and their structural model were constructed. The results showed that the inhibitors mainly depended on the hydrophobic interactions with the hydrophobic pockets I and II, and on the hydrogen-bonds with α-Thr178, α-Val181 and β-Cys241. According to their binding conformations, the structures of the inhibitors were divided into three parts, namely A, B and the bridge between them. The structural model of the inhibitor (the hydrophobic centers H1 and H2, the hydrophobic group H3, the hydrogen-bond acceptors A1 and A2 and the polar atom P) was built. The main factors of H1 and H2 are the volume size, and the planarity, while the bridge part should be in rigid form to maintain parts A and B to be in the same side of the bridge (in cis-conformation). A potential hydrogen-bond acceptor A3 was proposed between A2 and the loop area.

Key words: tubulin, colchicine, docking, binding mode, structural model