氧化石墨烯与蛋白质相互作用的分子机制研究

项目名称： 氧化石墨烯与蛋白质相互作用的分子机制研究

项目编号： No.11504032

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 周波

作者单位： 成都工业学院

项目金额： 21万元

中文摘要： 近年来，随着石墨烯工业的发展，尤其是在生物医药方面应用的发展，石墨烯对生物体尤其是对人体的安全性问题，也受到人们越来越多地关注。用于生物医药的石墨烯通常为氧化石墨烯；研究氧化石墨烯与蛋白质相互作用的分子机制，将有助于人们认识石墨烯潜在的生物毒性，但该机制仍不是十分清楚。本项目拟利用分子动力学模拟方法，结合生物物理学理论，深入研究氧化石墨烯与蛋白质相互作用的动力学过程及物理机制。研究内容包括：研究蛋白在氧化石墨烯基底上的粘附过程、粘附形态及驱动力；研究尺度较小的（氧化）石墨烯（如石墨烯量子点）与蛋白质的相互作用，考察石墨烯是否可以破坏蛋白质分子的结构，或是阻断蛋白―蛋白相互作用，或是作为配体与蛋白质分子的活性位点稳固结合（阻碍蛋白结合其天然配体，从而产生毒性）。本项研究有助于人们从分子水平上认识、理解（氧化）石墨烯潜在的生物毒性，也有望为人们设计基于石墨烯的新型生物传感器，提供理论借鉴。

中文关键词： 氧化石墨烯；蛋白质；纳米毒性；分子机制；分子动力学模拟

英文摘要： With rapid development of graphene industry and increasing biomedical applications of graphene in recent years, there are increasing concerns on the biological safety of graphene due to its unintended interactions with proteins and other biological molecules. The most commonly used graphene for bio-applications is graphene oxide (GO), not the pristine graphene. Understanding the molecular mechanism of the interaction between GO and proteins would be helpful to better assess the potential toxicity of graphene, but this mechanism is still not well understood so far. In this project, on the basis of all-atom molecular dynamics simulations together with the related biophysical theory, we will provide a deep investigation on the interaction between GO nanosheets and proteins, including the dynamical process of adsorption/binding and the underlying physical mechanism. The research contains two sections: i) Investigation on the adsorption of proteins on a GO surface, including the adsorption kinetics, final secondary and tertiary structures of proteins, and the origin of driving force. ii) Investigation on the interaction of proteins with small-sized GO nanosheets (such as graphene quantum dots). We will explore whether and how a small-sized GO nanosheet spontaneously disrupts the native structure of proteins, interrupts the protein-protein interactions, and wins the competitive binding on proteins over their native ligands (interrupting the regular binding of the ligand with the target protein, resulting in nanotoxicity). This research would be helpful to assess and better understand the potential toxicity of graphene at the molecular level, and provides a molecular basis for the novel design of graphene-based biosensors.

英文关键词： graphene oxide;protein;nanotoxicity;molecular mechanism;molecular dynamics simulations