Exploring the impact of F270V mutation in the β-tubulin (Bos Taurus) structure and its function: a computational perspective
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Paclitaxel is the most effective chemotherapeutic agent used for the treatment of a broad spectrum of solid tumors. However, observed paclitaxel resistance in clinical trials presents one of the major obstacles for cancer chemotherapy. Most importantly, resistance due to β-tubulin mutations (F270V) has been intensely debated in recent years. Despite all efforts, mechanism of resistance is still not well understood. In this study, computational techniques were employed to uncover the effect of F270V mutation in the β-tubulin structure and its function. The tools such as MuStab, CUPSAT and I-Mutant were employed to address the consequence of F270V mutation in the structural stability of β-tubulin. Further, molecular simulation study was employed to understand the functional impact of β-tubulin mutation. We believe that this study will provide useful guidance for the development of novel inhibitors that are less susceptible to drug resistance.
KeywordsF270V mutation Molecular docking Molecular dynamics Paclitaxel
The authors of the manuscript would like to thank the management of VIT University for providing the facility and support to carry out this research work. We sincerely thank reviewers for their valuable comments and suggestions for the improvement of this manuscript. The authors also thank Professor M.A. Mohamed Sahul Hameed, English division, for English editing and grammar corrections.
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