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

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资助。 在过去的几年里，已经看到了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机械性能。 目前最先进的技术涉及监测微操纵分子上的生化反应，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内的距离测量和皮牛顿范围内的力测量。 该项目的目标是发展这类研究蛋白质对DNA的组织的单分子力距实验的理论描述，并将这些想法应用于理解这类关于染色体的实验。要研究的具体类型的问题包括：大DNA分子被蛋白质折叠的平衡和非平衡方面，蛋白质结合到双螺旋上，然后扭曲双螺旋; DNA折叠对大DNA分子的拓扑状态的影响，作为细胞分裂期间复制DNA的解缠结如何与它们的折叠耦合的模型;响应于施加的力（包括由其他生物分子施加的力）的dsDNA或RNA螺旋环结构的打开和关闭的动力学; DNA位点之间的“通讯”过程的动力学，其中通讯通过DNA序列的并置或通过“信使”发生。连续访问两个位点的（通常是蛋白质）分子;在折叠染色体中发现的基于双链DNA的核蛋白丝网络的机械反应，以及通过序列定向切割对该反应的修饰。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资助。 在过去的几年里，已经看到了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机械性能。 目前最先进的技术涉及监测微操纵分子上的生化反应，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内的距离测量和皮牛顿范围内的力测量。 该项目的目标是发展这些单分子力距实验的理论描述，研究蛋白质对DNA的组织，并应用这些想法来理解这种类型的染色体实验。

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.***