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

这是一项由材料研究部和分子与细胞生物学部共同资助的理论基金。近年来，基于微操作技术研究单个和小分子生物分子力学特性的新技术得到了发展。目前最先进的技术包括对微操纵分子上的生化反应进行监测，从而得出生物分子机制运行的统计力学图像。这些类型的实验通常包括纳米范围内的距离测量和皮牛顿范围内的力测量。这个项目的目标是发展这种单分子力-距离实验的理论描述，这些实验研究DNA的蛋白质组织，并应用这些想法来理解这种类型的染色体实验。需要研究的具体问题类型包括：与双螺旋结构结合并扭曲的蛋白质折叠大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，作为细胞分裂过程中重复DNA的解缠与折叠耦合的模型；dsDNA或RNA螺旋环结构在外力作用下的打开和关闭动力学，包括其他生物分子的作用；DNA位点之间“通信”过程的动力学，其中通信通过DNA序列的并列发生，或者通过依次访问两个位点的“信使”（通常是蛋白质）分子进行；在折叠染色体中发现的基于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。这是一项由材料研究部和分子与细胞生物学部联合资助的理论基金。近年来，基于微操作技术研究单个和小分子生物分子力学特性的新技术得到了发展。目前最先进的技术包括对微操纵分子上的生化反应进行监测，从而得出生物分子机制运行的统计力学图像。这些类型的实验通常包括纳米范围内的距离测量和皮牛顿范围内的力测量。这个项目的目标是发展这种单分子力-距离实验的理论描述，这些实验研究DNA的蛋白质组织，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.***