Phase Behavior of Random Heteropolymers In Solution

众所周知，由DNA编码的蛋白质序列是其结构和功能的关键基础。大量的工作已经致力于合成序列特异性合成聚合物（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，它仍然是一个问题：“在合成聚合物中需要多大程度的序列特异性才能表现出蛋白质样行为？” 最近的实验研究表明，随机杂聚物（RHP）与统计序列控制可以设计概括蛋白质的功能。这与生物学中公认的蛋白质序列-结构-功能方法正交。拟议的研究旨在回答一个重要的问题，这些RHP是在不同的水平，从段，单链，集群的解决方案。从高分子相行为的角度进行系统的研究，将联合收割机与传统高分子科学和生物学的知识源泉相结合。成功的RHP开发可能使聚合物与生物过程分子界面，并最终导致杂化功能材料。该项目包括广泛的跨学科教育和指导方面，推广，本科实验室模块的发展，以及创建公开可用的软件工具，RHP序列模拟和分析，以克服RHP design.Part 2的初始障碍：技术总结RHP作为伴侣蛋白，以稳定酶在非天然环境和通道蛋白选择性，快速运输质子。 最近的研究结果表明，单体序列特异性不是复制天然蛋白质某些特性的先决条件。合理设计具有蛋白质样行为的RHP是可行的。该项目将在单链水平和整体水平上实验研究RHP的合成和溶液行为，并为初步了解这类复杂，具有挑战性和有用的聚合物材料提供实验基础。具体而言，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）RHP在稀溶液中的相行为;（3）RHP在浓度增加的溶液中的组装。 同时，PI的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在聚合物设计方面代表了很少探索的领域，并且包括作为关键设计参数的受控随机性。如果成功，计划中的研究将为合成真正的蛋白质样聚合物铺平道路。随着RHP方法的跨学科性质，这些研究提供了一个平台，以促进不同科学界之间的聚合物科学和下一代材料科学家的培训机会。 该项目包括广泛的跨学科教育和指导方面，推广，本科实验室模块的开发，以及为RHP序列模拟和分析创建公开可用的软件工具，以克服RHP设计中的初始障碍。该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估的支持。

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.