Entanglement in Biology -- How Nature Controls the Topology of Proteins

具有非平凡拓扑的蛋白质--打结蛋白质--在蛋白质折叠中提供了最大的挑战。因此，了解结点形成和稳定的机制将对我们理解蛋白质折叠和功能动力学产生重大影响。这个项目的重点是了解和表征在蛋白质的α/β结甲基转移酶家族中负责结子形成的潜在物理原理。研究将集中在家族的一个单体成员上，坚定地简化折叠分析。这种单体打结蛋白的发现将使我们能够剖析导致打结形成的潜在原理以及对蛋白质功能的影响。因此，这些研究将为未来的蛋白质设计工作提供基本的基础。更广泛的影响。这个项目架起了数学、生物、化学和物理领域的桥梁，激发了尖端的跨学科合作，并将在定义下一个十年折叠中的关键问题方面发挥重要作用。研究生将通过这项研究接触到化学、数学、物理和生物学，并将获得有价值的实验和理论技能(分子生物学、蛋白质生物化学、化学合成、配位化学、光谱技术、电化学、结晶学)，这些技能将更好地帮助他们在职业生涯的后期解决复杂的科学问题。该项目由物理系的生命系统物理学项目和分子和细胞生物科学系的分子生物物理学项目共同支持。

Proteins with non-trivial topology - knotted proteins - provide the greatest challenge in protein folding. Therefore, understanding the mechanisms of knot formation and stability will have a major impact on our understanding of protein folding and functional dynamics at large. This project is focused on understanding and characterizing the underlying physical principles responsible for knot formation in the alpha/beta knot methyltransferase family of proteins. Research will focus on a monomeric member of the family, firmly simplifying folding analyses. This discovery of a monomeric knotted protein will allow the dissection of the underlying principles that lead to knot formation and the impact on protein function. Consequently, these studies will provide the fundamental basis for future protein design efforts. BROADER IMPACT. This project bridges the fields of mathematics, biology, chemistry, and physics, inspiring cutting-edge interdisciplinary collaborations, and will be important in defining the key problems in folding for the next decade. Graduate students will be exposed to chemistry, mathematics, physics and biology through this study and will be provided with valuable experimental and theoretical skills (molecular biology, protein biochemistry, chemical synthesis, coordination chemistry, spectroscopic techniques, electrochemistry, crystallography) that will better assist them as they tackle complex scientific problems later in their careers.This project is being supported jointly by the Physics of Living Systems Program in the Physics Division and by the Molecular Biophysics Program in Division of Molecular and Cellular Biosciences.