Decoding the mechanism of disordered protein interactions

解读无序蛋白质相互作用的机制

• 批准号: 10708010
• 负责人: Wenwei Zheng
• 金额: $ 36.8万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10708010
• 关键词: Arizona; Biological; Biological Process; Biophysics; Collaborations; Communities; Computing Methodologies; Data; Disease; Goals; Grain; Liquid substance; Methodology; Methods; Modeling; Molecular; Molecular Conformation; Phase; Play; Polymers; Property; Proteins; Publications; Research; Resolution; Role; Structure; Students; Techniques; Universities; computerized tools; design; driving force; experimental group; flexibility; insight; interest; multi-scale modeling; novel; programs

Project Summary/Abstract Intrinsically disordered proteins (IDPs), which lack of a well-defined folded structure alone, play important roles in a variety of intracellular activities. This is usually made possible via a disorder-to-order transition when interacting with other biomolecules. However, there has been growing evidence towards the indispensable roles of conformational flexibility and dynamics on regulating biological activities. Zheng's lab focuses on investigating IDP interactions through developing multiscale computational modeling methods. Dr. Zheng has a track record of developing all-atom, coarse-grained and polymer models for IDPs with publications directly relevant to the research focuses. The lab has already contributed to modeling methods for interpreting experimental data of IDPs through collaborating with multiple experimental groups. The research program will be a good addition to the biophysics community within Arizona State University and provide research opportunities to students on this timely topic. The long-term goal of the group is to gain a comprehensive understanding of the driving force of disordered protein assemblies. Two interrelated research topics are proposed including (1) deciphering the role of flexible regions when an IDP interacts with its folded partner; and (2) investigating the mechanism of IDP-driven liquid-liquid phase separation (LLPS). The project combines computational methods in multiple resolutions with a variety of experimental techniques through three collaborations. Such unique combination of computational and experimental methods will provide an unprecedented level of insights on the molecular mechanism of IDP interactions. The designing of novel methodology framework for studying IDP assembly will benefit a broad range of audience interested in IDP relevant biological process.

项目总结/摘要 内源性无序蛋白（IDP）缺乏明确的折叠结构， 在各种细胞内活动中发挥重要作用。这通常是通过无序到有序 当与其他生物分子相互作用时。然而，越来越多的证据表明， 构象的灵活性和动力学在调节生物活性方面起着不可或缺的作用。Zheng的实验室 重点是通过开发多尺度计算建模方法来研究IDP的相互作用。 博士Zheng在为IDP开发全原子、粗粒度和聚合物模型方面有着良好的记录， 与研究重点直接相关的出版物。该实验室已经为建模方法做出了贡献 通过与多个实验小组合作，解释国内流离失所者的实验数据。的 研究计划将是一个很好的除了生物物理界在亚利桑那州州立大学和 为学生提供研究这一主题的机会。该集团的长期目标是获得 全面理解无序蛋白质组装的驱动力。两个相互关联 提出的研究课题包括：（1）当IDP与 （2）研究IDP驱动的液-液相分离（LLPS）机理。 该项目将多种分辨率的计算方法与各种实验技术相结合 通过三次合作。这种独特的计算和实验方法的结合将 为IDP相互作用的分子机制提供了前所未有的见解。的设计 研究IDP组装的新方法框架将使感兴趣的广泛受众受益， IDP相关的生物过程。