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

Abigail Knight博士（北卡罗来纳州查佩尔山大学）和Yaroslava Yingling博士（北卡罗来纳州州立大学）的目标是开发工具，以更好地了解蛋白质和蛋白质样分子的折叠和排列如何影响其与金属离子结合的能力。金属结合材料在水净化或金属结合疗法等应用中具有巨大的潜力，但设计仅与复杂环境中所需离子结合的材料，如水处理厂或生物流体，仍然是一个挑战。受天然金属结合蛋白的启发，该团队旨在生成实验和计算工具，以系统地研究如何控制肽的3D结构，以促进所需的金属结合特性。研究结果将为合成生物学，药物输送和纳米电子学中下一代材料的发展提供设计原则。将建立一个这类信息的数据库，以汇总这些研究活动产生的信息，并积极征求其他研究人员的意见。这一点，以及两个PI继续努力向公众宣传这项研究，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工程化到下一代材料中至关重要。然而，这些材料的合理设计是一个长期的挑战与障碍所产生的许多相互关联的属性有助于协调领域。该项目的重点是开发一个超分子平台，用于系统地评估肽构象对金属离子配位特异性和对目标金属离子亲和力的作用。金属蛋白模拟自组装材料是特别感兴趣的，因为超分子组装提供了一个模块化平台，用于调整表面曲率，从而构象，在金属结合位点的肽。这种迭代实验/计算研究的目标是提供一个基本的理解，如何组装的形态和肽构象有助于金属结合特异性，解锁金属离子稳态的规则，并提供深入了解蛋白质和材料的设计与复杂的金属结合配置文件。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，这有可能有助于克服从头设计金属蛋白质和多刺激响应材料的重大障碍。该项目的成果将被整合到一个数据库中，并提供给超分子组装和蛋白质模拟社区一个新的有价值的信息来源。该奖项反映了NSF的法定使命，并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，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.