Assessment of structural peculiarities of glaziovianin A interaction with human α-, β and γ-tubulins

  • P. A. Karpov
  • S. I. Spivak
  • O. V. Rayevsky
  • O. Yu. Nyporko
  • S. P. Ozheredov
  • Ya. B. Blume


Aim. To determine the features of the ligand-protein interaction of glaziovianin A and human α-, β- and γ-tubulin. Methods. Protein and ligand spatial structure modelling (I-Tasser, Grid), molecular docking (CCDC Gold), molecular dynamics simulation (GROMACS). Results. Using the method of molecular docking in CCDC Gold ligand-protein complexes of glaziovianin A and human α-, β- and γ-tubulin were reconstructed. Studied ligand interactions in GTP/GDP-exchange and colchicine binding sites of different tubulin isotypes. The built ligand-protein complexes were studied using molecular dynamics simulations. Conclusions. Binding of glaziovianin A with human tubulin was confirmed exposing its derivatives as perspective tubulin effectors. The binding energies of ligand-protein interaction confirm higher affinity for β-tubulin molecules, and it was suggested that glazovianin A binding may occur at two alternative sites: GTP/GDP-exchange site and site of colchicine binding.

Keywords: tubulin, glaziovianin A, binding, antitumor activity.


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