DNA Springs Coupled to Proteins

DNA 弹簧与蛋白质偶联

• 批准号: 1006162
• 负责人: Giovanni Zocchi
• 金额: $ 60万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1006162&HistoricalAwards=false
• 关键词: DNA; Springs; Coupled; Proteins

This award by the Biomaterials program in the Division of Materials Research to University of California Los Angeles is to build a fundamental understanding of the mechanochemistry of proteins and to calibrate the forces produced by DNA oligomers. The biological cell is a miniature chemical factory operated by molecular daemons called enzymes. Each daemon may speed up a specific chemical reaction enormously. The objective of this project is to learn how to control the daemons mechanically, ultimately achieving mechanical control of chemical reactions. Specifically, the project will use a ?molecular spring? to stress the enzyme, and measure the effect on the chemical reaction controlled by that enzyme. This study brings mechanical tools such as springs and levers to bear at the molecular scale, opening a new nanotechnology direction. Scientifically, it will build up our knowledge of the mechano-chemistry of enzymes. Several graduate students and one postdoctoral fellow will be trained in the experimental and theoretical methods of this emerging field, which cuts across disciplines from physics to chemistry to molecular biology and thus offers optimal opportunities to broaden the scientific outlook of young researchers. This research also provides a splendid opportunity to educate the public in these exciting developments in modern science, through public lectures, interactions with LA area teachers (through the facilities of California NanoSystem Institute), and web-based dissemination of important results. Enzymes as biological catalysts, couple mechanical motion and forces to chemical reactions through conformational transitions. Moving beyond structural descriptions, the objective of this project is to build a dynamic understanding of these complex structures, in terms of the elastic energies and forces which couple to the chemistry. Through a unique method which uses DNA as "molecular springs" attached to the enzyme, the investigators will apply controlled mechanical stresses to several proteins and measure the effect on the different steps which determine the reaction rate. Parallel experiments will answer the longstanding question of what is the elastic energy of sharply bent configurations of DNA, in other words, will calibrate the DNA springs. The knowledge will be applied to the parametrization of nonlinear models of DNA mechanics. This research explores fundamental physics at the boundary of chemistry and mechanics. It provides the vehicle for training graduate students and postdoctoral fellows in paradigm-changing biological physics research, both experimental and theoretical.

该奖项由加州大学洛杉矶分校材料研究部的生物材料项目授予，旨在建立对蛋白质机械化学的基本理解，并校准DNA低聚物产生的力。生物细胞是一个微型化学工厂，由称为酶的分子守护进程操作。每个守护进程都可以极大地加速特定的化学反应。这个项目的目标是学习如何机械地控制守护进程，最终实现化学反应的机械控制。具体而言，该项目将使用一个？分子泉对酶施加压力，并测量对该酶控制的化学反应的影响。这项研究将弹簧和杠杆等机械工具应用于分子尺度，开辟了一个新的纳米技术方向。科学上，它将建立我们对酶的机械化学的知识。几名研究生和一名博士后研究员将接受这一新兴领域的实验和理论方法的培训，该领域跨越从物理学到化学再到分子生物学的学科，从而为拓宽年轻研究人员的科学视野提供了最佳机会。这项研究还提供了一个极好的机会，教育公众在这些令人兴奋的发展，在现代科学，通过公开讲座，互动与洛杉矶地区的教师（通过加州纳米系统研究所的设施），并基于网络的传播的重要成果。酶作为生物催化剂，通过构象转变将机械运动和力耦合到化学反应中。超越结构描述，这个项目的目标是建立这些复杂结构的动态理解，在弹性能量和力耦合到化学。通过一种独特的方法，使用DNA作为附着在酶上的“分子弹簧”，研究人员将对几种蛋白质施加受控的机械应力，并测量对决定反应速率的不同步骤的影响。平行实验将回答长期存在的问题，即DNA急剧弯曲构型的弹性能是多少，换句话说，将校准DNA弹簧。这些知识将应用于DNA力学非线性模型的参数化。本研究探索化学和力学边界的基础物理学。它为培养研究生和博士后研究员提供了改变范式的生物物理学研究的工具，包括实验和理论。