Phase Behavior of Random Heteropolymers In Solution

无规杂聚物在溶液中的相行为

• 批准号: 2104443
• 负责人: Ting Xu
• 金额: $ 45.16万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2104443&HistoricalAwards=false
• 关键词: Phase; Behavior; Random; Heteropolymers; Solution

PART 1: NON-TECHNICAL SUMMARYIt is well accepted that a protein’s sequence encoded by DNA is the key foundation toward its structure and functions. Extensive efforts have been devoted to synthesis of sequence-specific synthetic polymers (oligomers and multi-block copolymers) and to probe how the changes in monomer sequence affect the polymer behavior. However, it remains as a question: “what extent of sequence specificity is needed in synthetic polymers to exhibit protein-like behavior?” Recent experimental studies demonstrated that random heteropolymers (RHPs) with statistical sequence control could be designed to recapitulate proteins’ functions. This is orthogonal to well accepted protein sequence-structure-function approaches in biology. The proposed studies aim to answer an important question on what these RHPs are at different levels ranging from segment, single-chain, to clusters in solution. Systematic studies from the angle of polymer phase behavior will combine the fountain of knowledge in traditional polymer science and biology. Successful RHP developments may enable polymers to molecularly interface with biological processes and ultimately lead to hybrid functional materials. The project includes broad interdisciplinary educational and mentoring aspects, outreach, development of undergraduate laboratory modules, as well as creation of publicly available software tools for RHP sequence simulation and analysis to overcome the initial barriers in RHP design.PART 2: TECHNICAL SUMMARYRHPs act as chaperon proteins to stabilize enzymes in non-native environments and channel proteins to selectively, rapidly transport protons. Recently results on such RHPs suggested that monomeric sequence specificity is not the prerequisite to replicate some properties of natural proteins. It is feasible to rationally design RHPs with protein-like behavior. This project will experimentally study the RHPs’ synthesis and solution behavior at the single-chain level and as ensembles and provide experimental foundation toward initial understanding of this class of complex, challenging, and useful polymeric materials. Specifically, the planned studies focus on: (1) Synthesis and characterization of RHP libraries with controlled composition and statistical monomer distribution; (2)Phase behavior of RHPs in dilute solutions; (3) Assemblies of RHPs in solutions with increased concentration. In parallel, the PI's group will synthesize and characterize model block copolymers to delineate effects of statistical monomer distribution in RHPs. As an orthogonal approach to sequence-specific polymers, RHPs represent a rarely explored area in terms of polymer design and encompass controlled randomness as a critical design parameter. If successful, the planned studies will pave the path toward truly protein-like polymers synthetically. With the interdisciplinary nature of RHP approach,these studies provide a platform to promote polymer science among different scientific communities and training opportunities for the next generation of materials scientists. The project includes broad interdisciplinary educational and mentoring aspects, outreach, development of undergraduate laboratory modules, as well as creation of publicly available software tools for RHP sequence simulation and analysis to overcome the initial barriers in RHP design..This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

第 1 部分：非技术摘要 人们普遍认为，DNA 编码的蛋白质序列是其结构和功能的关键基础。人们付出了大量的努力来合成序列特异性的合成聚合物（低聚物和多嵌段共聚物），并探索单体序列的变化如何影响聚合物的行为。然而，这仍然是一个问题：“合成聚合物需要什么程度的序列特异性才能表现出类似蛋白质的行为？” 最近的实验研究表明，可以设计具有统计序列控制的随机杂聚物（RHP）来概括蛋白质的功能。这与生物学中广泛接受的蛋白质序列-结构-功能方法正交。拟议的研究旨在回答一个重要问题，即这些 RHP 在解决方案中处于不同级别（从片段、单链到簇）。从聚合物相行为角度进行系统研究将结合传统高分子科学和生物学的知识源泉。成功的 RHP 开发可能使聚合物能够与生物过程进行分子界面，并最终产生混合功能材料。该项目包括广泛的跨学科教育和指导方面、推广、本科生实验室模块的开发，以及创建用于 RHP 序列模拟和分析的公共软件工具，以克服 RHP 设计中的初始障碍。第 2 部分：技术摘要 RHP 充当伴侣蛋白，以稳定非天然环境中的酶，并引导蛋白质选择性地快速传输质子。 最近对此类 RHP 的研究结果表明，单体序列特异性并不是复制天然蛋白质某些特性的先决条件。合理设计具有类蛋白质行为的RHP是可行的。该项目将通过实验研究 RHP 在单链水平和整体上的合成和溶液行为，并为初步了解此类复杂、具有挑战性和有用的聚合物材料提供实验基础。具体来说，计划的研究重点是：（1）具有受控组成和统计单体分布的RHP文库的合成和表征； (2)RHPs在稀溶液中的相行为； (3) RHP在浓度增加的溶液中的组装。 与此同时，PI 小组将合成和表征模型嵌段共聚物，以描述 RHP 中统计单体分布的影响。作为序列特异性聚合物的正交方法，RHP 代表了聚合物设计方面很少探索的领域，并将受控随机性作为关键设计参数。如果成功，计划中的研究将为合成真正的类蛋白质聚合物铺平道路。凭借RHP方法的跨学科性质，这些研究为在不同科学界之间推广高分子科学提供了平台，并为下一代材料科学家提供了培训机会。 该项目包括广泛的跨学科教育和指导方面、外展、本科生实验室模块的开发，以及创建用于 RHP 序列模拟和分析的公开软件工具，以克服 RHP 设计中的初始障碍。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。