Homology modelling, molecular dynamics simulation and docking evaluation of β-tubulin of Schistosoma mansoni.

Schistosomiasis is one of the neglected diseases causing considerable morbidity and mortality throughout the world. Microtubules with its main component, tubulin play a vital role in helminthes including schistosomes. Benzimidazoles represent potential drug candidates by binding β-tubulin. The study aimed to generate a homology model for the β-tubulin of S. mansoni using the crystal structure of O visaries (Sheep) β-tubulin (PDB ID: 3N2G D) as a template, then different β-tubulin models were generated and two previously reported benzimidazole derivatives (NBTP-F and NBTP-OH) were docked to the generated models, the binding results indicated that both S. mansoni, S. haematobium were susceptible to the two NBTP derivatives. Additionally, three mutated versions of S. mansoni β-tubulin wild-type were generated and the mutation (F185Y) seems to slightly enhance the ligand binding. Dynamics simulation experiments showed S. haematobium β-tubulin is highly susceptible to the tested compounds; similar to S. mansoni, moreover, mutated models of S. mansoni β-tubulin altered its NBTPs susceptibility. Moreover, additional seven new benzimidazole derivatives were synthesized and tested by molecular docking on the generated model binding site of S. mansoni β-tubulin and were found to have good interaction inside the pocket. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Fouad El-Shehabi, Basem Mansour, Waleed A Bayoumi, Serry A El Bialy, Mohammad A Elmorsy, Hassan M Eisa, Amira Taman. Homology modelling, molecular dynamics simulation and docking evaluation of β-tubulin of Schistosoma mansoni. Biophysical chemistry. 2021 Nov;278:106660

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PMID: 34482215

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