Defining Tertiary Structure with Designed Beta-Hairpins

这一建议旨在增加我们对蛋白质二级结构之间基本生物分子识别的理解，以确定高亲和力，高特异性三级相互作用的必要条件。我们将研究天然侧链之间的相互作用以及我们期望提供更高稳定性或特异性的非天然氨基酸。这项研究将为理解蛋白质-蛋白质相互作用提供重要的基础见解，并将为破坏蛋白质-蛋白质相互作用的需求提供关键见解。此外，这些研究将扩展可用于控制分子组装的分子识别支架集，并提供新的系统来创建定义良好的超分子结构，用于药物化学，从头设计和材料化学中的各种应用。在教育方面，这项研究也具有广泛的影响。通过实践研究，文献讨论，跨学科课程，与该领域的研讨会演讲者互动，以及在会议上的演讲，该研究计划将教育研究生和本科生有机，生物和生物物理化学，为日益跨学科的科学劳动力提供强大的跨学科背景

This proposal aims to increase our understanding of fundamental biomolecular recognition between protein secondary structures to determine the necessary requirements for high affinity, high specificity tertiary interactions. We will investigate interactions between naturally occurring sidechains as well as unnatural amino acids that we expect will provide higher stability or specificity. This research will provide important fundamental insights into the understanding of protein-protein interactions and will provide critical insight into requirements for disrupting protein-protein interactions. In addition, these studies will expand the set of molecular recognition scaffolds available for controlling molecular assembly and provide new systems to create well-defined supramolecular structures for a variety of applications in medicinal chemistry, de novo design, and materials chemistry.With regard to education, this research also has broad impact. Through hands-on research, discussion of the literature, interdisciplinary courses, interaction with seminar speakers in the field, and presentations at conferences, this research program will educate both graduate and undergraduate students in organic, biological, and biophysical chemistry, providing a strong interdisciplinary background which is necessary in the increasingly interdisciplinary scientific workforce