Towards the identification of the binding site of benzimidazoles to β-tubulin of Trichinella spiralis: insights from computational and experimental data.

摘要: Benzimidazole-2-carbamate derivatives (BzC) are among the most important broad-spectrum anthelmintic drugs for treatment of nematode infections. BzC selectively bind to β-tubulin monomer and inhibit microtubule polymerization. However, crystallographic structure tubulin mechanism action still unknown. Moreover, relation between binding site has not yet been explained accurately. By using amino acid sequence Trichinella spiralis as a basis by applying homology modeling techniques, we were able build 3D this protein. In order identify BzC, molecular docking dynamics calculations carried out with model. The results in good agreement common mutations associated drug resistance (F167Y, E198A F200Y) experimental competitive inhibition colchicine tubulin. Besides, Glu198, Thr165, Cys239 Gln134 identified acids process since they directly interact formation hydrogen bonds. presented paper step further towards understanding, at level, mode drugs. These constitute valuable information design or improvement more potent selective molecules.