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 beta-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 beta-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 beta-tubulin. Further, molecular simulation study was employed to understand the functional impact of beta-tubulin mutation. We believe that this study will provide useful guidance for the development of novel inhibitors that are less susceptible to drug resistance.