Study On The Interaction Between A Series Of Podophyllotoxin Analogues And Tubulin By Molecular Dynamics Simulation

Cancer represent one of the most common human diseases that seriously threaten the life of people with sharply increasing number of morbidity and mortality attributed to a combination of factors:contamination, stressfulness and unhealthy lifestyle, making it urgent to take efficacious measures to prevent tumor under higher standards.As an important cellular component in all the eukaryotic cells, tubules have many key biological functions including mitosis. And this important physiological function makes microtubule protein attractive object of relevent studies in treatment of various malignant tumors. For function of tubule being closely bound up with its stability, disruption of tubule’s dynamic balance and cell mitosis has been proven an significant way in anticancer drug design. Microtubule As targets of anti-tumor drugs is through the use of the dynamic characteristics, which have anti-cancer effect. Podophyllotoxin and derivatives belonging to natural medicines possessing an outstanding anti-tumour activities, mainly prescribed for anti-cancer therapeutical effects through interacting with tubulin.In this dissertation, targeting on Colchicine sites, Molecular Dynamics was mainly used to investigate the binding modes between tubulin and a series of Podophyllotoxin analogues, which contributes to designing anti-tumor drugs with better effects.This dissertation contains two parts:Chapter Ⅰ:The structures, functions and traits of tubulins were briefly introduced. The discovery and distribution, structure and modfication, pharmacological function and antitumor effect of podophyllotoxin and analogues were summarized. This paper expounded the screening of antitumor drugs, present methods and status of antitumor drugs. Basic theoretical approach of molecular docking and molecular dynamics simulation were introduced.Chapter2:Interaction and relevant binding models of tubulins and Podophyllotoxin Analogues were analysized based on molecular docking and molecular dynamics simulation, and the binding free energy was carried out to expound properties of the colchicine sites which also provides significant information for modification of podophyllotoxin analogues.