Theory and application of polyelectrolyte complexation

[852353]聚电解质和带相反电荷的物质之间的相互作用产生各种自组装结构，在工业环境、医疗保健和生物学中很常见。虽然有大量关于多电解质络合的实验工作，但开发可靠的理论工具来描述其潜在的结构和热物理性质却远远落后。这些理论预测不仅对工程应用很重要，而且对理解涉及带相反电荷的生物大分子结合的基本生物过程也很重要。本研究旨在建立从分子角度定量分析聚电解质复合物结构和热力学稳定性的预测模型。理论模型将通过分子模拟和表征良好的实验系统的结果进行验证。还提出了一个案例研究，以应用理论工具来理解病毒衣壳中的基因组包装。智力优势：本研究中使用的理论技术是建立在PI小组最近在发展和应用经典密度泛函理论（DFT）方面的工作基础上的。DFT为描述复杂分子体系的微观结构和界面行为提供了统一的计算工具。初步研究表明，它能够捕获局部封装和长距离静电和链内相关性，这对于成功描述强电荷聚电解质系统至关重要。计划的研究重点是开发互补的分子模型，以研究多电解质复合物的结构和相变。如果成功，这项工作的成果将为理解不同的分子自组装过程开辟新的途径，从而将改变合成和天然聚电解质系统的工业设计和实践。更广泛的影响：在这项工作中提出的理论技术的通用性质承诺不仅应用于多电解质系统，而且应用于更广泛的复杂流体领域。特别是，先进计算方法的发展可能对理解病毒复制周期的分子基础的基础研究产生不同寻常的影响，病毒复制周期通常需要DNA/RNA链与带相反电荷的多肽或蛋白质的强相互作用。这种理解对于确定治疗病毒引起的传染病的潜在药物靶点和制定有效的基因/生物制药卫生保健提供系统至关重要。该项目将为青年科学家提供获得跨学科研究经验的机会，并激发他们在分子建模和工程方面的职业兴趣。除了支持一名高级研究生获得高级学位外，该项目还将通过提供基于研究的论文项目，从大学荣誉计划（UHP）招募至少两名本科生。PI计划以该研究相关的介绍资料为基础，准备介绍病毒自组装和基因传递的最新进展的讲座和特别研讨会。除了UHP之外，这些介绍性材料也将用于大学快速启动暑期学院项目，该项目专为渴望从事生物医学和工程职业的高中生设计

0852353WuInteraction between polyelectrolytes and oppositely charged substances results in various self assembled structures commonplace in industrial settings, health care, and biology. While there is a large body of experimental work on polyelectrolyte complexation, much lagged behind is development of a reliable theoretical tool to describe the underlying structure and thermophysical properties. The theoretical predictions are important not only for engineering applications but also for understanding fundamental biological processes that involve association of oppositely charged biomacromolecules. The proposed research seeks to develop predictive models useful for quantifying structure and thermodynamic stability of polyelectrolyte complexes from a molecular perspective. The theoretical models will be validated with results from molecular simulations and well characterized experimental systems. A case study is also proposed to apply the theoretical tools for understanding genome packaging in viral capsids.Intellectual merit: The theoretical techniques to be used in this research are built uponrecent work in the PI's group in development and application of classical density functional theory (DFT). DFT provides a unifying computational tool for describing the microscopic structure and interfacial behavior of complex molecular systems. Preliminary investigations have demonstrated that it is able to capture both the local packaging and long range electrostatic and intra chain correlations essential for a successful description of strongly charged polyelectrolyte systems. The planned research focuses on development of complementary molecular models for investigating the structure and phase transitions of polyelectrolyte complexes. If successful, accomplishments from this work may open new avenues for understanding diverse molecular self assembly processes and thereby will transform industrial design and practice of both synthetic and natural polyelectrolyte systems.Broader impacts: The generic nature of the theoretical techniques proposed in this work promises applications not only to polyelectrolyte systems but also to the broader fields of complex fluids. In particular, development of advanced computational methods may have unusual impacts in fundamental research toward understanding the molecular basis of viral replication cycle that often entails strong interactions of DNA/RNA chains with oppositely charged polypeptides or proteins. Such understanding is essential for identification of potential drug targets for treatment of virus induced contagious diseases and for formulation of efficient gene/biopharmaceuticals health care delivery systems.This project will provide opportunity for young scientists to gain interdisciplinary research experience and motivate their career interests in molecular modeling and engineering. In addition to supporting one senior graduate student toward his/her advanced degree, this project will recruit at least two undergraduate students from the University Honors Program (UHP) by offering research based thesis projects. Based on the introductory materials related to this research, the PI plans to prepare lectures and special seminars to introduce recent developments in viral self assembly and gene delivery. In addition to UHP, the introductory materials will also be used for the university FastStart summer academy program, designed for high-school students who aspire to biomedical and engineering careers