Theory of Single-Molecule Study of Biomolecule Interactions and Chromosome Structure

这是一项由材料研究和分子与细胞生物学部门联合资助的理论资助。在过去的几年里，基于微操作技术的新技术的发展，以研究单个和少量生物分子的力学性质。目前最先进的技术包括对微操作分子上的生化反应进行监控，从而产生生物分子机械操作的统计机械图。这些类型的实验通常涉及纳米范围的距离测量和皮牛顿范围的力测量。这个项目的目标是发展这种研究蛋白质组织DNA的单分子力-距离实验的理论描述，并应用这些想法来理解这种类型的合体实验。要研究的具体类型包括：与双螺旋结合并随后扭曲双螺旋的蛋白质折叠大DNA分子的平衡和非平衡方面；DNA折叠对大DNA分子拓扑状态的影响，作为在细胞分裂过程中复制的DNA如何解缠耦合到其折叠的模型；DsDNA或RNA螺旋环结构在外力作用下打开和关闭的动力学，包括由其他生物分子施加的力；DNA位点之间的“通信”过程的动力学，其中这种通信通过DNA序列的并列发生，或者通过一个‘信使’(通常是蛋白质)分子顺序访问两个位点；在折叠的染色体中发现的基于dsDNA的核蛋白细丝网络的机械响应，以及通过序列定向切割对该响应的修改。%这是由材料研究和分子与细胞生物学部门联合资助的理论拨款。在过去的几年里，基于微操作技术的新技术的发展，以研究单个和少量生物分子的力学性质。目前最先进的技术包括对微操作分子上的生化反应进行监控，从而产生生物分子机械操作的统计机械图。这些类型的实验通常涉及纳米范围的距离测量和皮牛顿范围的力测量。这个项目的目标是发展这些研究蛋白质组织DNA的单分子力-距离实验的理论描述，并应用这些想法来理解这种类型的联体实验。

This is a theoretical grant funded jointly by the Divisions of Materials Research and Molecular and Cellular Biology. The past few years have seen the development of new techniques based on micromanipulation technology to study the mechanical properties of single and small numbers of biomolecules. Current state-of-the-art involves the monitoring of biochemical reactions on micromanipulated molecules, leading to a statistical mechanical picture of the operation of biomolecular machinery. These types of experiments typically involve distance measurements in the nanometer range, and force measurements in the piconewton range. The objective of this project is to develop theoretical descriptions of these kind of single-molecule force-distance experiments that study the organization of DNA by proteins, and to apply those ideas to understand experiments of this type on chomosomes.Specific types of problems to be studied include: equilibrium and nonequilibrium aspects of folding of large DNA molecules by proteins which bind to, and then distort, the double helix; effects of DNA folding on the topological state of large DNA molecules, as a model for how disentanglement of duplicated DNAs is coupled to their folding during cell division; kinetics of opening and closing of dsDNA or RNA helix-loop structures in response to applied forces, including those applied by other biomolecules; kinetics of 'communication' processes between DNA sites, where that communication occurs through juxtaposition of DNA sequences, or alternatively through a 'messenger' (typically protein) molecule which sequentially visits two sites; mechanical response of networks of dsDNA-based nucleoprotein filaments as found in folded chromosomes, and the modification of that response by sequence-directed cutting.%%%This is a theoretical grant funded jointly by the Divisions of Materials Research and Molecular and Cellular Biology. The past few years have seen the development of new techniques based on micromanipulation technology to study the mechanical properties of single and small numbers of biomolecules. Current state-of-the-art involves the monitoring of biochemical reactions on micromanipulated molecules, leading to a statistical mechanical picture of the operation of biomolecular machinery. These types of experiments typically involve distance measurements in the nanometer range, and force measurements in the piconewton range. The objective of this project is to develop theoretical descriptions of these kind of single-molecule force-distance experiments that study the organization of DNA by proteins, and to apply those ideas to understand experiments of this type on chomosomes.***