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

具有非平凡拓扑结构的蛋白质-打结蛋白质-为蛋白质折叠提供了最大的挑战。因此，了解结形成和稳定性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。该项目的重点是了解和表征负责结形成的α/β结甲基转移酶蛋白质家族的基本物理原理。研究将集中在家庭的单体成员，坚定地简化折叠分析。这一发现的单体打结蛋白质将允许解剖的基本原则，导致结的形成和蛋白质功能的影响。因此，这些研究将为未来的蛋白质设计工作提供基础。更广泛的影响。该项目连接了数学、生物学、化学和物理学领域，激发了前沿的跨学科合作，并将在未来十年内定义折叠的关键问题。研究生将通过这项研究接触化学、数学、物理和生物学，并将获得宝贵的实验和理论技能（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）这将更好地帮助他们在以后的职业生涯中解决复杂的科学问题。这个项目是由物理学联合支持的。物理系生命系统项目和分子与细胞生物科学系分子生物物理项目。

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.