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Theoretical Studies of Protein-Protein and Protein-DNA Binding Rates

Title: Theoretical Studies of Protein-Protein and Protein-DNA Binding Rates.
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Name(s): Alsallaq, Ramzi A., author
Zhou, Huan-Xiang, professor directing dissertation
Blaber, Michael, outside committee member
Berg, Bernd, committee member
Rikvold, Per Arne, committee member
Xiong, Peng, committee member
Department of Physics, degree granting department
Florida State University, degree granting institution
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2007
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Proteins are folded chains of amino acids. Some of the amino acids (e.g. Lys, Arg, His, Asp, and Glu) carry charges under physiological conditions. Proteins almost always function through binding to other proteins or ligands, for example barnase is a ribonuclease protein, found in the bacterium Bacil lus amyloliquefaceus. Barnase degrades RNA by hydrolysis. For the bacterium to inhibit the potentially lethal action of Barnase within its own cell it co-produces another protein called barstar which binds quickly, and tightly, to barnase. The biological function of this binding is to block the active site of barnase. The speeds (rates) at which proteins associate are vital to many biological processes. They span a wide range (from less than 103 to 108 M-1 s-1 ). Rates greater than ~106 M -1s-1 are typically found to be manifestations of enhancements by long-range electrostatic interactions between the associating proteins. A different paradigm appears in the case of protein binding to DNA. The rate in this case is enhanced through attractive surface potential that effectively reduces the dimensionality of the available search space for the diffusing protein. This thesis presents computational and theoretical models on the rate of association of ligands/proteins to other proteins or DNA. For protein-protein association we present a general strategy for computing protein-protein rates of association. The main achievements of this strategy is the ability to obtain a stringent reaction criteria based on the landscape of short-range interactions between the associating proteins, and the ability to compute the effect of the electrostatic interactions on the rates of association accurately using the best known solvers for Poisson-Boltzmann equation presently available. For protein-DNA association we present a mathematical model for proteins targeting specific sites on a circular DNA topology. The main achievements are the realization that a linear DNA with reflecting ends and specific site in the middle of the chain is kinetically indistinguishable from its circularized topology, and the ability to predict the effect of the dissociation via the ends of linear DNA on the rate of association which is to reduce the rate.
Identifier: FSU_migr_etd-0182-P (IID)
Submitted Note: A Dissertation submitted to the Department of Physics in partial fulfillment of the requirements for the degree of Doctor of philosophy.
Degree Awarded: Spring Semester, 2007.
Date of Defense: April 4, 2007.
Keywords: Electrostatic Enhancement, Energy Landscape, Facilitated Diffusion, Transition-State Theory, Binding Rate, Protein-DNA Association, Protein-Protein Association, Brownian Dynamics Simulations
Bibliography Note: Includes bibliographical references.
Advisory Committee: Huan-Xiang Zhou, Professor Directing Dissertation; Michael Blaber, Outside Committee Member; Bernd Berg, Committee Member; Per Arne Rikvold, Committee Member; Peng Xiong, Committee Member.
Subject(s): Physics
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_migr_etd-0182-P
Owner Institution: FSU

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Alsallaq, R. A. (2007). Theoretical Studies of Protein-Protein and Protein-DNA Binding Rates. Retrieved from http://purl.flvc.org/fsu/fd/FSU_migr_etd-0182-P

Title: Theoretical Studies of Protein-Protein and Protein-DNA Binding Rates.
Name(s): Alsallaq, Ramzi A., author
Zhou, Huan-Xiang, professor directing dissertation
Blaber, Michael, outside committee member
Berg, Bernd, committee member
Rikvold, Per Arne, committee member
Xiong, Peng, committee member
Department of Physics, degree granting department
Florida State University, degree granting institution
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2007
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Proteins are folded chains of amino acids. Some of the amino acids (e.g. Lys, Arg, His, Asp, and Glu) carry charges under physiological conditions. Proteins almost always function through binding to other proteins or ligands, for example barnase is a ribonuclease protein, found in the bacterium Bacil lus amyloliquefaceus. Barnase degrades RNA by hydrolysis. For the bacterium to inhibit the potentially lethal action of Barnase within its own cell it co-produces another protein called barstar which binds quickly, and tightly, to barnase. The biological function of this binding is to block the active site of barnase. The speeds (rates) at which proteins associate are vital to many biological processes. They span a wide range (from less than 103 to 108 M-1 s-1 ). Rates greater than ~106 M -1s-1 are typically found to be manifestations of enhancements by long-range electrostatic interactions between the associating proteins. A different paradigm appears in the case of protein binding to DNA. The rate in this case is enhanced through attractive surface potential that effectively reduces the dimensionality of the available search space for the diffusing protein. This thesis presents computational and theoretical models on the rate of association of ligands/proteins to other proteins or DNA. For protein-protein association we present a general strategy for computing protein-protein rates of association. The main achievements of this strategy is the ability to obtain a stringent reaction criteria based on the landscape of short-range interactions between the associating proteins, and the ability to compute the effect of the electrostatic interactions on the rates of association accurately using the best known solvers for Poisson-Boltzmann equation presently available. For protein-DNA association we present a mathematical model for proteins targeting specific sites on a circular DNA topology. The main achievements are the realization that a linear DNA with reflecting ends and specific site in the middle of the chain is kinetically indistinguishable from its circularized topology, and the ability to predict the effect of the dissociation via the ends of linear DNA on the rate of association which is to reduce the rate.
Identifier: FSU_migr_etd-0182 (IID)
Submitted Note: A Dissertation submitted to the Department of Physics in partial fulfillment of the requirements for the degree of Doctor of philosophy.
Degree Awarded: Spring Semester, 2007.
Date of Defense: April 4, 2007.
Keywords: Electrostatic Enhancement, Energy Landscape, Facilitated Diffusion, Transition-State Theory, Binding Rate, Protein-DNA Association, Protein-Protein Association, Brownian Dynamics Simulations
Bibliography Note: Includes bibliographical references.
Advisory Committee: Huan-Xiang Zhou, Professor Directing Dissertation; Michael Blaber, Outside Committee Member; Bernd Berg, Committee Member; Per Arne Rikvold, Committee Member; Peng Xiong, Committee Member.
Subject(s): Physics
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_migr_etd-0182
Owner Institution: FSU