Cellular Crowding Effects of Biomolecular Stability and Dynamics

生物分子稳定性和动力学的细胞拥挤效应

• 批准号: 1330560
• 负责人: Michael Feig
• 金额: $ 70.59万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1330560&HistoricalAwards=false
• 关键词: Cellular; Crowding; Effects; Biomolecular; Stability

Intellectual Merit:Cellular environments consist of dense, heterogeneous solutions of biomolecules that differ significantly from the dilute, homogeneous conditions typically considered in structural biology. A consideration of the resulting crowding effects is essential to fully understand biomolecular function in cellular environments. Simulations with realistic models of cellular proteins and nucleic acids are used to examine the physicochemical effects of crowding. The main goal is to better understand the role of intermolecular interactions and altered solvent properties on biomolecular stability upon crowding. The simulations carried out involve models ranging from fully atomistic explicit solvent representations to multi-scale models where solvent and/or crowders are modeled in a simplified fashion. The results from the simulations are essential for developing effective models of cellular environments that are unavailable at the time but urgently needed for large-scale simulations of cellular dynamics.Broader Impacts:The broader impact to society will be a more comprehensive understanding of cellular processes from a physical perspective. More specifically, the research aims to connect the detailed molecular-level understanding of biology to processes occurring on cellular and systems levels. Ultimately, such insight will allow the development of detailed in silico cellular models based on physical principles that can be queried to understand complex biological processes. A number of more specific broader impacts will be catalyzed by the research proposed here: Interdisciplinary training of students at the interface of physical, biological, and computational sciences, both graduate students and teams of undergraduate students from physical and biological sciences; promotion of the involvement of women; focused efforts to recruit undergraduates from underrepresented minorities through the IDEAS program at MSU; enhancement of widely used modeling software; promotion of an international collaboration with RIKEN in Japan including short-term research visits abroad for students involved in the project; and broad dissemination of research results through traditional channels as well as public outreach through public presentations to lay audiences.

智力优势：细胞环境由生物分子的稠密、异质溶液组成，与结构生物学中通常考虑的稀释、均匀条件有显著差异。考虑到由此产生的拥挤效应对于充分理解细胞环境中的生物分子功能至关重要。模拟与现实的细胞蛋白质和核酸的模型被用来检查拥挤的物理化学效应。主要目标是更好地理解分子间相互作用和改变的溶剂性质对拥挤时生物分子稳定性的作用。所进行的模拟涉及的模型范围从完全原子的明确的溶剂表示的多尺度模型，其中溶剂和/或拥挤以简化的方式建模。模拟的结果对于开发有效的细胞环境模型至关重要，这些模型在当时尚不可用，但对于细胞动力学的大规模模拟来说却迫切需要。更广泛的影响：对社会的更广泛影响将是从物理角度更全面地了解细胞过程。更具体地说，该研究旨在将生物学的详细分子水平理解与细胞和系统水平上发生的过程联系起来。最终，这种洞察力将允许基于物理原理开发详细的计算机细胞模型，这些模型可以被查询以了解复杂的生物过程。一些更具体的更广泛的影响将催化这里提出的研究：学生在物理，生物和计算科学的接口，研究生和本科生团队从物理和生物科学的跨学科培训;促进妇女的参与;集中精力通过在密歇根州立大学的IDEAS计划，从代表性不足的少数民族招收本科生;加强广泛使用的建模软件;促进与日本理化学研究所的国际合作，包括参与该项目的学生到国外进行短期研究访问;通过传统渠道广泛传播研究成果，并通过向非专业观众进行公开演讲进行公众宣传。