Collaborative Research: Probing Coordination Specificity of Metalloprotein Domains with Peptide-Polymer Amphiphile Self Assembly

在化学系大分子、超分子和纳米化学项目的支持下，北卡罗来纳大学教堂山分校的Abigail Knight博士和北卡罗来纳州立大学的Yarola va Yingling博士致力于开发工具，更好地了解蛋白质和蛋白质类分子的折叠和排列如何影响它们与金属离子的结合能力。金属结合材料在水净化或金属结合疗法等方面具有巨大的应用潜力，但设计在水处理厂或生物流体等复杂环境中仅与所需离子结合的材料仍然是一个挑战。受天然金属结合蛋白的启发，该团队的目标是开发实验和计算工具，系统地研究如何控制多肽的3D结构，以促进所需的金属结合特性。研究结果将为下一代材料在合成生物学、药物输送和纳米电子学方面的进步提供设计原则。除了积极征集其他研究人员的贡献外，还将建立一个这类信息的数据库，以汇总从这些研究中产生的信息。这一点，加上两个PI继续努力向公众传达这项研究，将最大限度地发挥这项工作的影响。金属离子的受控配位对于将复杂功能设计成下一代材料至关重要。然而，这些材料的合理设计是一个长期的挑战，许多相互关联的性质导致了配位领域的障碍。本项目致力于开发一个超分子平台，用于系统评价多肽构象对金属-离子配位的特异性和对目标金属离子的亲和力的作用。模拟金属蛋白的自组装材料特别令人感兴趣，因为超分子组装提供了一个模块化的平台，用于调节金属结合位置上的多肽的表面曲率，从而调节其构象。这种迭代的实验/计算研究的目的是提供一个基本的理解，了解组装的形态和多肽构象如何有助于金属结合的特异性，解锁金属离子的动态平衡规则，并提供对具有复杂金属结合轮廓的蛋白质和材料的设计的洞察。这些结果将使人们更深入地了解大分子构象对金属结合选择性和亲和力的作用，这可能有助于克服金属蛋白质和多刺激响应材料从头设计中的重大障碍。这项提议的产品将被整合到一个数据库中，并向超分子组装和蛋白质模拟社区提供一个新的有价值的信息来源。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Dr. Abigail Knight (University of North Carolina, Chapel Hill) and Dr. Yaroslava Yingling (North Carolina State University) aim to develop tools to better understand how the folding and arrangement of protein and protein-like molecules impacts their ability to bind to metal ions. Metal binding materials have significant potential for applications such as water purification or metal-binding therapies but designing materials that bind only to the requisite ions in complex environments, such as water treatment plants or biological fluids, remains a challenge. Inspired by natural metal-binding proteins, the team aims to generate experimental and computational tools to systematically study how to control the 3D structure of a peptide to promote desired metal binding properties. The research findings will provide design principles for the advancement of next generation materials within synthetic biology, drug delivery, and nanoelectronics. A database of this information will be created to aggregate the information generated from these pursuits in addition to the active recruitment of contributions from other researchers. This, alongside the continuing efforts of both PIs to communicate this research to the public, will maximize the impact of this work.Controlled coordination of metal ions is critical for engineering complex functions into next generation materials. However, rational design of these materials is a longstanding challenge with obstacles arising from many interrelated properties contributing to the coordination spheres. This project focuses on the development of a supramolecular platform for systematically evaluating the role of peptide conformation on the specificity of metal-ion coordination and affinity for target metal ions. Metalloprotein-mimetic self-assembled materials are of particular interest as the supramolecular assembly provides a modular platform for tuning the surface curvature, and thus conformation, of peptides in a metal-binding site. The goal of this iterative experimental/computational study is to provide a fundamental understanding of how the assembled morphology and peptide conformation contribute to metal binding specificity, unlocking rules of metal ion homeostasis and providing insight into the design of proteins and materials with complex metal-binding profiles. The results will enable a deeper understanding of the role of macromolecule conformation on metal binding selectivity and affinity, which has the potential to help overcome significant hurdles in the de novo design of metallo-proteins and multi-stimuli responsive materials. The products of this proposal will be integrated into a database and to make available to the supramolecular assembly and protein-mimetic communities with a new source of valuable information.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.