Decoding the mechanism of disordered protein interactions

项目摘要/摘要 固有无序蛋白(IDPs)本身缺乏明确的折叠结构，发挥作用 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的方式来实现的 与其他生物分子相互作用时的过渡性。然而，越来越多的证据表明， 构象灵活性和动力学在调节生物活性方面发挥着不可或缺的作用。郑氏实验室 重点是通过开发多尺度计算建模方法来研究IDP相互作用。 郑博士在为国内流离失所者开发全原子、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。该实验室已经对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。这个 研究计划将是亚利桑那州立大学生物物理学社区的一个很好的补充 为学生提供关于这一及时主题的研究机会。该集团的长期目标是获得 全面了解蛋白质组装紊乱的驱动力。两个相互关联的 提出的研究主题包括：(1)当IDP与IDP交互时，解密灵活区域的作用 (2)研究IDP驱动的液液相分离的机理。 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 对IDP相互作用的分子机制提供了前所未有的洞察力。该系统的设计与实现 研究IDP组装的新方法框架将使对以下内容感兴趣的广泛受众受益 IdP相关生物过程。

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.