Novel anti-tubulin agents from plant and marine origins: insight from a molecular modeling and dynamics study

The screening of a variety of botanical species and marine organisms provided satisfactory novel tubulin binding agents (TBAs). The current study aims to quantify the binding capabilities of several TBAs including vinca alkaloids, colchicine and other taxol-domain binding agents with microtubule. The stability of the bound complexes and detailed interactions within the active site are the endeavor of the study. Different natural extracts reported as TBAs, have been screened against the refined structure of ab-tubulin hetero-dimers using ligand docking. The molecular dynamics simulation of the best-docked poses for 50 ns demonstrates that molecules 7 (discodermolide) and 10 (laulimalide) exhibit better tendencies of binding with the microtubule. Average RMSD analysis and dynamical pathway observations indicate that these molecules transit quickly to a dynamically stable configuration and seem to achieve a comfort zone by remaining stable throughout the dynamics. The results obtained, may form the foundation for the future synthesis and evaluation of new compounds with potential tubulin binding properties.