LEAPS-MPS:Revealing Key Residues and Physical Interactions Drive the Structural and Dynamic Changes in Subdomains of PICK1

LEAPS-MPS：揭示关键残基和物理相互作用驱动PICK1子域的结构和动态变化

• 批准号: 2137558
• 负责人: Yi He
• 金额: $ 24.62万
• 依托单位: University of New Mexico
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2137558&HistoricalAwards=false
• 关键词: LEAPS; MPS; Revealing; Key; Residues

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). In this project, funded by the Mathematical and Physical Sciences Directorate and housed in the Chemistry Division, Professor Yi He and their students at the University of New Mexico (UNM) will use computational methods to study the structural and mechanical properties of PICK1, a biomolecule that plays a role in a large number of diseases, including breast cancer, schizophrenia, addiction, and addiction relapse. Prof. He also plans broadening participation activities in which they would emphasize the utility of PICK1 as a potential drug target to treat substance use disorder as a framework for outreach. They will involve URM students in research, develop activities that will facilitate integration of students across educational levels (including undergraduate and graduate students at UNM, which is a minority serving institution, MSI), and participate in outreach activities at regional primarily undergraduate institutions and high schools.Professor He will computationally probe the key residues and physical interactions associated with the structural and mechanical properties of each subdomain that is directly related to the biological function of PICK1 (Protein Interacting with C Kinase-1). Computational tools will be used to probe two key molecular domains of PICK1, PDZ and BAR. Prof. He will also optimize the United-RESidue (UNRES) physics-based coarse-grained force field to explore the disordered linker which connects the PDZ and BAR domain. Understanding the biological role of each subdomain will lay the foundation to explore how nature assembles signaling proteins through modular domains. These goals will ultimately be achieved by applications of advanced physics-based atomistic and coarse-grained simulations, which can now reach the relevant timescales for small proteins.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项是根据2021年《美国救援计划法》（公法117-2）全部或部分资助的。 在这个项目中，由数学和物理科学局资助并在化学部门中安置，YI教授和他们的新墨西哥大学的学生（UNM）将使用计算方法研究PICK1的结构和机械性能，这是一种生物分子，在包括大量疾病中起作用的生物分子，包括乳腺癌，包括乳腺癌，棘手，互相构成，并相互作用，并在内。 他还计划扩大参与活动，在这些活动中，他们将强调Pick1作为将药物使用障碍作为外展框架的潜在药物靶标的实用性。 他们将使URM学生参与研究，开展活动，以促进跨教育水平的学生整合（包括UNM的本科生和研究生，即UNM的本科生和研究生，这是少数派服务机构，MSI），并参与区域本科机构的宣传活动，主要是与高中的互动相关的，他将在各种范围内与ProProtions computical Is computical Is Is Is suptoriation Is Is Is Is Is Is Is Is Is Is Is Is Is Is Is Is Is Insuption Is Is Is Is Is Is Is Is Is Is Is Intimation Is Is Is Is Insutions相关性相关联相关Pick1（蛋白质与C激酶-1相互作用）。 计算工具将用于探测pick1，pdz和bar的两个关键分子域。 他还将优化基于物理的统一残留（UNRER RER RER RER RES），以探索连接PDZ和BAR域的无序接头。 了解每个子域的生物学作用将奠定基础，以探索自然如何通过模块化结构域组装信号蛋白。这些目标最终将通过基于高级物理学的原子和粗粒的模拟来实现，该模拟现在可以到达有关小蛋白质的相关时间尺度。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛影响的审查标准通过评估来获得支持的。

项目成果

AlphaFold illuminates half of the dark human proteins.

• DOI: 10.1016/j.sbi.2022.102372
• 发表时间: 2022-06
• 期刊: CURRENT OPINION IN STRUCTURAL BIOLOGY
• 影响因子: 6.8
• 作者: Binder, Jessica L.;Berendzen, Joel;Stevens, Amy O.;He, Yi;Wang, Jian;Dokholyan, Nikolay, V;Oprea, Tudor, I
• 通讯作者: Oprea, Tudor, I