原癌基因C-erbB-2太赫兹介电特性及弛豫模型解析研究

There has been an increased interest in exploring the effects of THz dielectric properties of multi-molecular interaction events in the liquids, of particular interest is to explore the mathematical model of the structural and functional characteristics of antigen-antibody interaction. Using the broad bandwidth THz dielectric spectroscopic, this project provided an appropriate method to extract the dynamical characteristic parameters and build a uniform model of theoretical calculations to investigate the interaction between the C-erbB-2 oncogene (antigen) and its antibody. Focusing on the key scientific issues to be resolved, the following research is intended to be undertaken: 1) Based on the mathematic analytic of detailed molecular structure determination, the dynamics properties and the dielectric information, we aim to build a dielectric relaxation model for antigen and antigen-antibody in solutions, in order to clarify the effects of THz complex dielectric constant non-linear key factors caused by antigen conformation, and predict the terahertz sensitive groups on the surface of antigen with the critical recognition features. 2) In addition, we will build a novel interface electrodynamics model for antigen-antibody interaction to understand how to use the molecular multi-dimensional potential energy surface function to describe the change of antigen molecular configuration, which reveal the dynamics characteristics of the structural of antibodies binding to antigen specificity. 3) Furthermore, by modeling and comparing the dielectric properties of the reactants and reaction products overexpression, we will clarify the mechanisms of lesions in clinic from the level of molecular electric properties. This basic research, which has the significant benefits on investigating the interaction between the receptor and ligand bonding, the specific reaction and the molecular recognition in the biomolecular system, hopefully can provide the theoretical foundation and the research method for a target-tumor therapy and an anti-cancer drug treatment by changing the internal electrical characteristics of biological systems using electromagnetic radiation.

为实现太赫兹频段液相多分子事件的电特征参数分析，解决抗原-抗体相互作用的结构及功能信息的数理模型解析，本项目采用动态检测原癌基因C-erbB-2及其与抗体相互作用的宽带太赫兹介电频谱解析方法：1) 通过对体系内部细微结构、动力学和介电信息的数学解析，建立抗原及抗原-抗体多分子事件的介电弛豫模型，明确抗原结构影响THz复介电常数非线性变化的关键因素，预测抗原-抗体表面具有关键识别功能的太赫兹敏感基团；2) 建立抗原-抗体复杂相界面电动力学模型，通过分子多维势能面函数随分子构型的变化规律，论证抗体对抗原高特异性结合的结构电动力学特征；3) 确定系统反应物及反应产物过表达的介电特异性参数，从分子电特性水平阐明相关重大疾病的病变机制。该方法可推广应用于生物分子受体与配体键合、特异性反应及分子识别等方面，为以改变生物系统内部电特性为靶向的肿瘤电磁辐射治疗和抗癌药物治疗提供可借鉴的理论基础和研究方法。

太赫兹（THz）辐射是近年来新兴的一种远红外相干辐射，太赫兹光谱在某些生物大分子的结构和动力学特性检测方面有着巨大潜力，可以弥补传统红外光谱技术对于整个分子构型、构象的细微变化不够敏感的不足。在近代研究分子微观结构的众多方法中，介电频谱分析方法可实现重大疾病的早期辅助性诊断，其主要原因在于：这种介电特征的变化更早于病理形态学变化。本项目研究在太赫兹频段采用介电频谱分析方法，从电信息角度提取生物分子结构及微环境的变化，则无需回避液相环境的局限。此外，THz介电频谱解析方法，能够有效提取生物系统内部微细结构的动力学和介电信息，特别是研究非均匀相体系太赫兹频谱特征参数解析方法，建立液相蛋白质复杂相的太赫兹介电模型，对拓展太赫兹技术在生物医学领域的应用，具有重要的方法学意义。利用本课题的相关研究方法，已实现血凝素蛋白的检出率比传统ELISA方法高出10倍，该方法可实现抗原-抗体免疫反应的无标记，快速、高灵敏度检测，对于解决现有的检测方法检测时间长、检测效率低的问题具有理论价值和潜在应用前景。.项目按照计划进度正常执行，实际经费支出与预算基本相符，执行期间项目负责人发表论文共计11篇，其中包括《Journal of Biomedical Optics》、《PLoS ONE》等SCI期刊论文6篇，EI论文5篇，申请国家发明专利2项（实审），软件著作权3项，超过预期目标。