Exploring tubulin-paclitaxel binding modes through extensive molecular dynamics simulations.

ABSTRACT: Cancer treatment remains a pressing challenge, with paclitaxel playing a pivotal role in chemotherapy by disrupting mitotic spindle dynamics through microtubule stabilization. However, the molecular details of paclitaxel interaction with β-tubulin, its target, remain elusive, impeding efforts to overcome drug resistance and optimize efficacy. Here, we employ extensive molecular dynamics simulations to probe the binding modes of paclitaxel within tubulin protofilaments. Our simulations reveal a spectrum of paclitaxel binding poses, correlated with conformational changes in neighboring residues, proposing the ligand (un)binding route. These diverse binding modes exhibit varied interaction patterns and binding energies, elucidating the complex interplay between paclitaxel-tubulin interactions

SUBMITTER: Bozdaganyan M 

PROVIDER: S-EPMC11897383 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature