Abstract

The discovery of numerous tubulin–binding anticancer agents raises the question of how and where the different agents bind on tubulin affect their antimitotic property. Antimitotic of vinblastine families binding site inhibit microtubule assembly. The ultimate action of this agent causes mitotic arrest by inhibiting normal dynamic instability at very low concentration. The investigation of vinblastine has been studied by theoretical methods. It has been established as the best structural and functional of vinblastine. In an effort to understand the conformational preferences that may be attributed to stereoelectronic effects, a number of computational chemistry studies carried out. Molecular mechanics, Monte Carlo, Molecular Dynamics and Langevin calculations have been performed on vinblastine. These results show the minimized structure of vinblastine, calculated potential energy for important dihedral angles and the effect of temperature on geometry of optimized structure. However, the vinblastine compound has been displayed different spectrum of gas phase and solvent NMR by GIAO and CSGT approximations, which appears the results of the determination of the number of active sites in vinblastine using the Onsager method that the O29 has the most shifting at indicated model and it has been reflected mostly the transfer of vinblastine to a less polar environment. These simulations provide an atomistic analysis of the vinblastine strategy and its implications for further investigations of microtubule.

Key words: Vinblastine, Monte Carlo, molecular dynamic, Langevin dynamic, NMR, DFT.