Structural Basis and Mechanism for Vindoline Dimers Interacting with α,β-Tubulin.

ABSTRACT: Vinblastine and its derivatives used in clinics as antitumor drugs often cause drug resistance and some serious side effects; thus, it is necessary to study new vinblastine analogues with strong anticancer cytotoxicity and low toxicity. We designed a dimer molecule using two vindoline-bonded dimer vindoline (DVB) and studied its interaction with α,β-tubulin through the double-sided adhesive mechanism to explore its anticancer cytotoxicity. In our work, DVB was docked into the interface between α-tubulin and β-tubulin to construct a complex protein structure, and then it was simulated for 100 ns using the molecular dynamics technology to become a stable and refined complex protein structure. Based on such a refined structure, the quantum chemistry at the level of the MP2/6-31G(d,p) method w

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC6682054 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature