Protein Dynamics in Complex Environments

复杂环境中的蛋白质动力学

• 批准号: 0613643
• 负责人: Martin Gruebele
• 金额: $ 93.78万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0613643&HistoricalAwards=false
• 关键词: Protein; Dynamics; Complex; Environments

As the protein folding field matures, more complex questions can be tackled. In living organisms, proteins interact with other proteins and nucleic acids, with cellular or extracellular matrices, and with membranes. Fundamental biophysical research is now poised to study this next generation of problems, while maintaining its thrust of using carefully chosen model systems to provide quantitative answers to biological questions. This project will focus on three areas involving biomolecular interactions. A new approach will study the dynamical interplay of folding with protein-protein binding and aggregate formation by designing proteins tethered together so their proximity can be controlled. A second thrust involves the design of membrane protein model systems ranging from simple helices to more complex bundles, to study the interaction of proteins with membranes during folding and insertion. The sequence of processes that lead to stable membrane protein structures will be elucidated in real time. The third area of biomolecular interactions concerns folding of proteins in crowded environments. Proteins dynamics will be studied in highly crowded matrices of proteins and carbohydrates by combining non-fluorescent thermophilic protein matrices with mesophilic probe proteins embedded in the matrix.This research project provides an important link between in vitro and in vivo studies, and a link to computational work on protein-environment interactions relevant to binding, signaling, and survival of proteins in the cell. This is achieved by developing new model systems less complex than the in vivo environment, yet far more complex than in traditional biophysical in vitro studies, and thus within reach of computational biology. Graduate and undergraduate students will receive training at the interface of physics, chemistry and biology, learning by approaches that combine instrumentation, molecular biology, and computational modeling. New US and international collaborations will further enhance the educational value of the research projects. Student-centered research will be complemented by an all-volunteer educational project. The biophysics curriculum at UIUC needs to be re-tooled to meet the needs of students at the interface between biology, instrumentation-oriented physical sciences, and in particular computational modeling, which is now an indispensable part of biophysics. The goal is to create a biophysics and computational biology curriculum for the 21st century, while involving faculty and student volunteers from the ground up. This project is jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences and the Experimental Physical Chemistry Program in the Division of Chemistry in the Mathematical and Physical Sciences Directorate.

随着蛋白质折叠领域的成熟，可以解决更复杂的问题。 在生物体中，蛋白质与其他蛋白质和核酸、细胞或细胞外基质以及膜相互作用。 基础生物物理学研究现在准备研究下一代问题，同时保持其使用精心选择的模型系统为生物学问题提供定量答案的主旨。 该项目将集中在涉及生物分子相互作用的三个领域。 一种新的方法将研究折叠与蛋白质-蛋白质结合和聚集体形成的动态相互作用，方法是设计蛋白质拴在一起，以便控制它们的接近程度。 第二个推力涉及膜蛋白模型系统的设计，从简单的螺旋到更复杂的束，以研究折叠和插入过程中蛋白质与膜的相互作用。 导致稳定的膜蛋白结构的过程的顺序将在真实的时间阐明。 生物分子相互作用的第三个领域涉及蛋白质在拥挤环境中的折叠。 通过将非荧光嗜热蛋白质基质与包埋在基质中的嗜温探针蛋白相结合，在蛋白质和碳水化合物的高度拥挤基质中研究蛋白质动力学。该研究项目提供了体外和体内研究之间的重要联系，以及与细胞中蛋白质结合，信号传导和存活相关的蛋白质-环境相互作用的计算工作的联系。 这是通过开发新的模型系统来实现的，该模型系统比体内环境更简单，但比传统的生物物理体外研究复杂得多，因此在计算生物学的范围内。 研究生和本科生将接受物理，化学和生物学接口的培训，通过联合收割机仪器，分子生物学和计算建模相结合的方法学习。 新的美国和国际合作将进一步提高研究项目的教育价值。 以学生为中心的研究将得到一个全志愿者教育项目的补充。 UIUC的生物物理学课程需要重新调整，以满足学生在生物学，仪器导向的物理科学，特别是计算建模，这是现在生物物理学不可或缺的一部分之间的接口的需求。 其目标是创建一个生物物理学和计算生物学课程的21世纪世纪，同时涉及教师和学生志愿者从地面上。该项目由生物科学理事会分子和细胞生物科学部的分子生物物理学和数学和物理科学理事会化学部的实验物理化学计划共同支持。