Theory and Application of Polyelectrolyte Complexation

项目编号：1404046机构：加州大学河滨分校标题：聚电解质络合的理论与应用本项目旨在计算聚电解质的特性，这些特性是生物医学相关系统的核心，如药物传递、基因敲除和病毒复制。计算的目标是建立一种新的计算程序，能够预测在各种水条件下聚电解质配合物的原子结构、热力学稳定性和环境响应。此外，PI将寻求验证计算，不仅仅是通过与高度理想化的实验系统进行比较，而是实际预测多肽-多肽相互作用等系统的性质，否则无法用传统的计算方法完成。这是一个雄心勃勃的提议，可以对生物学和生物医学重要分子系统的基本理解（以及因此的合理设计）产生重大影响，从而可以设计改进的药物输送系统和基于基因的技术。目前，大多数现有的研究都是基于传统的聚合物理论，忽略了局部密度不均匀性、明显的溶剂效应以及长链内和静电相关性。聚合物体系的简化表示有助于建立复杂形成的基本规则，以及块状聚电解质体系相行为的定性或偶尔的半定量特征。但是，平均场方法预测的低分辨率结构和体相变往往不足以描述实际应用所需的结构-活性关系。开发可靠的计算工具来预测反向带电聚合物之间的相互作用远远落后于实际应用。为了解决这些缺陷，本提案将尝试通过建立在PI小组在经典密度泛函理论（DFT）框架内的高通量自由能计算的最新进展基础上的理论方法来推进对聚电解质形成的理解，该理论将使用本工作中提出的新摄动方法推广到聚合物体系。该项目的目标是建立一种新的计算程序，能够预测在各种水条件下聚电解质复合物的原子结构、热力学稳定性和环境响应。此外，PI将寻求验证理论，不仅仅是通过与高度理想化的实验系统进行比较，而是实际预测复杂分子系统的性质，例如多肽-多肽相互作用，否则无法用传统的计算方法完成。拟议的工作还将确定和检查影响siRNA（小干扰RNA）稳定性和递送效率的热力学，siRNA是一种用于敲除特定基因的RNA。

PI: Wu, Jianzhong Proposal Number: 1404046 Institution: University of California-Riverside Title: Theory and Application of Polyelectrolyte ComplexationThis proposal seeks to calculate the properties of polymeric electrolytes that are central to bio-medically relevant systems, such as drug delivery, gene knockout, and viral replication. The goal of the computations is to establish a new calculational procedure capable of predicting the atomistic structure, thermodynamic stability, and environmental responses of polyelectrolyte complexes under various aqueous conditions. In addition, the PI will seek to validate the calculations, not just by comparison to highly idealized experimental systems, but to actually predict the properties of such systems as polypeptide-polypeptide interactions, which cannot otherwise be accomplished with conventional computational methods. This is an ambitious proposal that can have a significant impact on the fundamental understanding (and therefore rational design) of biologically and bio-medically important molecular systems that can lead to the design of improved drug delivery systems and gene-based technologies.At present, most of existing studies are based on conventional polymer theories that ignore local density inhomogeneity, explicit solvent effects, and long-ranged intra-chain and electrostatic correlations. The simplistic representations of the polymeric systems are useful to establish the basic rules of complex formation as well as qualitative or occasionally semi-quantitative features of the phase behavior of bulk polyelectrolyte systems. But the low-resolution structure and bulk phase transitions predicted by mean-field methods are often insufficient to describe the structure-activity relationships desired for practical applications. Development of reliable computational tools to predict the interaction between oppositely charged polymers lags far behind practical applications. In order to address these deficiencies, this proposal will attempt to advance the understanding of polyelectrolyte formation via a theoretical approach built upon recent progress from the PI's group on high-throughput free-energy calculations within the framework of the classical density functional theory (DFT), which will be generalized for polymeric systems using a new perturbation method proposed in this work. The goal of this project is to establish a new computational procedure capable of predicting the atomistic structure, thermodynamic stability, and environmental responses of polyelectrolyte complexes in various aqueous conditions. In addition, the PI will seek to validate the theory, not just by comparison to highly idealized experimental systems, but to actually predict the properties of complex molecular systems, such as polypeptide-polypeptide interactions, that cannot otherwise be accomplished with conventional computational methods. The proposed work will also identify and examine the thermodynamics that affect the stability and delivery efficacy of siRNA (small interfering RNA), a type of RNA used for knock-down of specific genes.