Thermodynamic and Molecular Dynamic Study of Physical and Chemical Stabilities on Microtubules Structure during Assembling and Disassembling

Abstract

Since microtubules stabilities as tubulin polymers for various activities in a cell depend on several items such as Stathmin, GTP hydrolysis, and Taxol, by this research assembling ↔ disassembling affected by these major parts have been accomplished via docking a molecular simulation in one frame, simultaneously. Different models have been proposed that link the tubulin heterodimer nucleotide content and the role of GTP hydrolysis with microtubule assembly and dynamics. Here, we used Monte Carlo simulation for thermodynamics data of microtubule assembly. In addition, for a novel and comprehensive research of micro-tubule structure in one image frame simultaneously, we simulated the alpha and beta tubulin structures, sthatmin curvature as well as GTPs, MAPs according to dynamics behavior during interactions with other cell components in microtubule. We also modeled various systems including one molecule stathmin interacts with four subunits tubulins (βαβα) for building a tight ternary complex, interaction between Taxol with β-tubulin {T-β}(PDB ID: 7TUB) and αβ-tubulin tetramers in the presence of stathmin curvature {T-(S-βαβα)} (PDB ID: 1 FFX), as well as with α,β-tubulin dimers (DB ID: 1TUB){T-(α,β)} in lack of stathmin, finally, with alpha-beta tubulin tetramers (DB ID: 6WVR) in lack of stathmin {T-(βαβα)} through docking and molecular dynamic simulation for any further comparison. Since large concentrations of free β in plasma solution increase the risk of cancer, it should be reduced and should be packed quickly with a dynamic reaction. By this work, we exhibited the H–F hydrogen bonding can decrease the free β tubulin in plasma. Fluorine atom in Taxol increases the effectiveness of this drug for treatment of some cancer diseases. Finally, the average RMSD and timeline of interactions confirmed the stability of complexes during dynamics structure of microtubule.