Crowding and Confinement in the Ribosome Exit Tunnel and Beyond

核糖体出口隧道及其他区域的拥挤和限制

• 批准号: 7650205
• 负责人: Samuel Cho
• 金额: $ 5.01万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-19 至 2010-07-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7650205
• 关键词: Address; Biological; Biological Models; Cells; Cereals; Cessation of life; Code; Complex; Crowding; Disease; Environment; Failure; Lead; Left; Mediating; Microscopic; Modeling; Peptides; Process; Proteins; RNA; RNA-Binding Proteins; RNA-Protein Interaction; Research; Ribosomes; Simulate; Structure; Water; Work; base; molecular dynamics; physical model

DESCRIPTION (provided by applicant): Project Summary: How biomolecules behave and interact with partners in its crowded environment must be considered for any realistic representation of biomolecular interactions in the cell. A model system that captures these important features of the cell is the ribosome exit tunnel. As a protein becomes synthesized by the ribosome, the newly formed nascent peptide chain must traverse a narrow tunnel in the ribosome, which is composed of a myriad of RNA, protein, and water molecules. In our proposed research, we will study the dynamics of a nascent peptide chain as it traverses the ribosome exit tunnel using a coarse-grained representation of the surrounding RNA and protein molecules. We will address the interactions of the nascent peptide chain with the heterogeneous mixture of biomolecules in the confined environment. Once the protein leaves the ribosome exit tunnel, we will study how the protein avoids aggregation that will lead to disease and death due to a failure to perform its function. We will begin by developing a physical-bioinformatical based recognition code of proteins and RNA interactions that takes into consideration water-mediated interactions. The code will be introduced into coarse-grained physical models for detailed molecular dynamics simulations of protein-RNA complexes. The next step will be to simulate a nascent peptide as it traverses through the crowded ribosome exit tunnel, which is comprised of the RNA and protein molecules. We will focus where in the crowded tunnel and under what conditions the nascent peptide chain may form secondary structure. Finally, we will simulate multiple nascent peptide chains to address how the protein chains in high concentration do not aggregate. Relevance: A physical, microscopic view of biological interactions in the cell is fundamental to our understanding of underlying processes. We will develop coarse-grained models to study the protein-RNA interactions to study how a newly formed protein leaves the ribosome to perform its function. Failure to successfully leave the proximity of the ribosome will lead to an inability of the cell to work, leading to disease and death.

描述（由申请人提供）： 项目摘要：为了细胞中生物分子相互作用的任何真实表现，必须考虑生物分子在拥挤的环境中如何表现以及与伙伴相互作用。捕获细胞这些重要特征的模型系统是核糖体出口隧道。当核糖体合成蛋白质时，新形成的新生肽链必须穿过核糖体中的狭窄隧道，核糖体由无数 RNA、蛋白质和水分子组成。在我们提出的研究中，我们将使用周围 RNA 和蛋白质分子的粗粒度表示来研究新生肽链穿过核糖体出口隧道时的动力学。我们将解决新生肽链与受限环境中生物分子的异质混合物的相互作用。一旦蛋白质离开核糖体出口通道，我们将研究蛋白质如何避免聚集，而聚集会因无法发挥其功能而导致疾病和死亡。我们将首先开发一种基于物理生物信息的蛋白质和 RNA 相互作用的识别代码，其中考虑到水介导的相互作用。该代码将被引入粗粒度物理模型中，以对蛋白质-RNA 复合物进行详细的分子动力学模拟。下一步将模拟新生肽穿过拥挤的核糖体出口隧道，该隧道由 RNA 和蛋白质分子组成。我们将重点关注在拥挤的隧道中的何处以及在什么条件下新生肽链可以形成二级结构。最后，我们将模拟多个新生肽链，以解决高浓度的蛋白质链如何不聚集的问题。相关性：细胞中生物相互作用的物理微观视角对于我们理解潜在过程至关重要。我们将开发粗粒度模型来研究蛋白质-RNA 相互作用，从而研究新形成的蛋白质如何离开核糖体来发挥其功能。未能成功离开核糖体附近将导致细胞无法工作，从而导致疾病和死亡。