分子动力学模拟HPV(16,18)E6蛋白

Molecular Dynamics Simulation of E6-protein in HPV Type 16,18

目的:对人乳头瘤病毒HPV16,18中E6蛋白结构进行分子模拟和分析,寻找可以作为蛋白-配体相互作用的关键结构区域。方法:以HPV16 E6蛋白为模板,对HPV18 E6蛋白进行同源建模,对构建的HPV18 E6模型以及晶体结构模型HPV16 E6进行分子动力学模拟,通过微观上的loop环分析和宏观上的整体运动分析研究了HPV18 E6与HPV16 E6在溶剂环境下结构变化的异同。结果:发现靠近N端loop环在蛋白-配体结合过程中能介导控制配体、水、离子进出的"门控"的作用,解释了两个蛋白在水溶剂中的运动构象的变化。结论:本研究解释了HPV16 E6与HPV18 E6两个蛋白在溶剂中的运动机制,并发现了loop环在其中扮演"门控"的作用,解释了两个蛋白在水溶剂中的运动构象的变化,该发现能够为基于两个蛋白为靶点的药物设计提供理论依据。

Objective： To search for the key regions used as protein-ligand interactions by simulating and analyzing the E6 protein structure of HPV16 and 18. Methods： The HPV16 E6 protein was used as a template for homology modeling of HPV18 E6 protein, the crystal structure model of HPV（18, 16） E6-protein was studied by molecular dynamics simulation. By analyzing the microscopic loop and the macroscopic motion, we study the similarities and differences of structural changes of HPV18 E6 and HPV16 E6 in aqueous solvents. Results： The results indicated loop in the N-terminal region played a role of ＂gatekeeper＂that could mediate ligand, water and ion in the process of protein-ligand interactions and reveal the changes of the conformation of two proteins in aqueous solvents.Conclusions： The movement mechanisms of HPV18 E6 and HPV16 E6 in aqueous solvents, as well as the role of loop that acting as a ＂gatekeeper＂ were elucidated. Meanwhile, these simulation results interpret the changes of the conformation of two proteins in aqueous solvents and provide theoretical basis for drug design based on two proteins.