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

University Of Illinois At Chicago, Chicago IL

Investigators

Abstract

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. ***