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Macroscopic modeling and dynamic sim...

Huang, Jing.

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Macroscopic modeling and dynamic simulations of supercoiled DNA with bound proteins.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Macroscopic modeling and dynamic simulations of supercoiled DNA with bound proteins./
Author:	Huang, Jing.
Description:	187 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-09, Section: B, page: 4333.
Contained By:	Dissertation Abstracts International64-09B.
Subject:	Chemistry, Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3105876
ISBN:	0496534432

Macroscopic modeling and dynamic simulations of supercoiled DNA with bound proteins.
Huang, Jing.

Macroscopic modeling and dynamic simulations of supercoiled DNA with bound proteins. - 187 p.

Source: Dissertation Abstracts International, Volume: 64-09, Section: B, page: 4333.

Thesis (Ph.D.)--New York University, 2003.

General methods are presented for modeling and simulating DNA molecules with bound proteins on the macromolecular level. The work is motivated by the need for accurate and affordable methods to simulate slow processes (on millisecond timescale) in large supercoiled DNA with or without proteins, such as the large-scale motions involved in the Hin-mediated inversion. We first improve modeling methods and simulation algorithms for long DNA to make them applicable for a large range of salt concentrations, including physiological conditions. We thus introduce inhomogeneous potentials for DNA/protein complexes based on available atomic-level structures. Electrostatically, we describe a DNA/protein complex as a set of optimized effective charges. We also introduce directional bending potentials as well as non-identical bead hydrodynamics. These models account for basic elements of protein binding effects on DNA local structures while are also computationally tractable. With this economical, macroscopic model, we perform Brownian dynamics simulations to analyze large-scale DNA motions in processes where DNA and proteins are intimately coupled. To validate these models and methods, we reproduce various properties measured by both Monte Carlo methods and experiments. We apply the developed models to investigate the two-site juxtaposition process and its dependence on the DNA superhelicity and salt in protein-free supercoiled DNA. We report for the first time an unexpected and potentially significant finding that the mechanism of site juxtaposition depends critically on the salt concentration. Our studies show that near physiological salt conditions, the "slithering" motion, or the bidirectional motion along DNA superhelices, is the dominant mechanism of site juxtaposition, rather than random collisions; the latter was thought to be the dominant mechanism under physiological conditions. We then study the Hin-mediated inversion system. By simulating a supercoiled DNA system with or without bound proteins, we observe significant effects of protein binding on global conformations and long-time dynamics of the DNA on the kilobasepair length scale. Further investigations of the kinetic pathways provide explanations on the mechanism and rate by which protein-bound DNA sites come in close spatial proximity and show that the topological selectivity and enhancer sequence of supercoiled DNA play critical roles in regulating the inversion reaction.

ISBN: 0496534432Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Macroscopic modeling and dynamic simulations of supercoiled DNA with bound proteins.
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245 1 0 $a Macroscopic modeling and dynamic simulations of supercoiled DNA with bound proteins.
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500 $a Source: Dissertation Abstracts International, Volume: 64-09, Section: B, page: 4333.
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502 $a Thesis (Ph.D.)--New York University, 2003.
520 $a General methods are presented for modeling and simulating DNA molecules with bound proteins on the macromolecular level. The work is motivated by the need for accurate and affordable methods to simulate slow processes (on millisecond timescale) in large supercoiled DNA with or without proteins, such as the large-scale motions involved in the Hin-mediated inversion. We first improve modeling methods and simulation algorithms for long DNA to make them applicable for a large range of salt concentrations, including physiological conditions. We thus introduce inhomogeneous potentials for DNA/protein complexes based on available atomic-level structures. Electrostatically, we describe a DNA/protein complex as a set of optimized effective charges. We also introduce directional bending potentials as well as non-identical bead hydrodynamics. These models account for basic elements of protein binding effects on DNA local structures while are also computationally tractable. With this economical, macroscopic model, we perform Brownian dynamics simulations to analyze large-scale DNA motions in processes where DNA and proteins are intimately coupled. To validate these models and methods, we reproduce various properties measured by both Monte Carlo methods and experiments. We apply the developed models to investigate the two-site juxtaposition process and its dependence on the DNA superhelicity and salt in protein-free supercoiled DNA. We report for the first time an unexpected and potentially significant finding that the mechanism of site juxtaposition depends critically on the salt concentration. Our studies show that near physiological salt conditions, the "slithering" motion, or the bidirectional motion along DNA superhelices, is the dominant mechanism of site juxtaposition, rather than random collisions; the latter was thought to be the dominant mechanism under physiological conditions. We then study the Hin-mediated inversion system. By simulating a supercoiled DNA system with or without bound proteins, we observe significant effects of protein binding on global conformations and long-time dynamics of the DNA on the kilobasepair length scale. Further investigations of the kinetic pathways provide explanations on the mechanism and rate by which protein-bound DNA sites come in close spatial proximity and show that the topological selectivity and enhancer sequence of supercoiled DNA play critical roles in regulating the inversion reaction.
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