Flexibility and Kinesin Affinity of Paclitaxel Stabilized Microtubule Under the Influence of GHz Electric Fields: A Molecular Modeling Approach

Abstract

Paclitaxel, one of the cancer chemotherapy drugs, stabilizes microtubule (MT) and changes its physical properties. Alteration in physical properties of MT and affinity of its associated motor proteins, such as kinesin, may be used as an effective approach in cancer treatment. In this paper, simultaneous influences of paclitaxel and oscillating GHz electric fields on flexibility of MT and on kinesin affinity to αβ-tubulin have been investigated, via using molecular dynamics simulation method. To approach to these purposes, a designed system consists of two αβ-tubulin stabilized by paclitaxel (SP αβ-tubulin) was exposed to electric fields in 1–10 GHz frequency range to examine MT flexibility. Then, another designed system was considered to study kinesin affinity to SP αβ-tubulin in three different structures, containing ATP, ADP and none of them. It was found that application of such fields changes flexibility of MT and changes kinesin affinity to SP αβ-tubulin. This variation in MT flexibility and kinesin affinity, due to the application of such fields, may perturb cancer treatment process, using paclitaxel.