Applications of a double-stranded elastic rod model to DNA / Jaspreet Singh.

Format:

Book

Thesis/Dissertation

Author/Creator:

Jaspreet Singh, author.

Contributor:

University of Pennsylvania. Department of Mechanical Engineering and Applied Mechanics, degree granting institution.

Purohit, Prashant K., degree supervisor.

Language:

English

Subjects (All):

Mechanical engineering.

Biophysics.

Statistical physics.

Mechanical engineering and applied mechanics--Penn dissertations.

Penn dissertations--Mechanical engineering and applied mechanics.

Local Subjects:

Mechanical engineering.

Biophysics.

Statistical physics.

Mechanical engineering and applied mechanics--Penn dissertations.

Penn dissertations--Mechanical engineering and applied mechanics.

Genre:

Academic theses.

Physical Description:

1 online resource (120 pages)

Contained In:

Dissertations Abstracts International 81-10B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2020.

Language Note:

English

System Details:

Mode of access: World Wide Web.

text file

Summary:

This thesis discusses the development and applications of a double-stranded elastic rod model for DNA, henceforth called \extit{birod} model. The model highlights the role of DNA elasticity in allosteric interactions between two ligands bound to DNA (chapters 3 and 4) and--combined with statistical mechanics--provides insights into the micromechanics of DNA melting (chapter 5).In chapters 3 and 4, the birod model for DNA is used to compute the allosteric interaction energy between two ligands on DNA. This interaction is quantified by measuring the change in free energy as a function of the distance between the binding sites for two ligands. The trends in this interaction energy can be explained using the birod model which accounts for the helical shape of DNA, elastic deformation of strands and base-pairs, and the stacking energy due to perturbations in position and orientation of the bases caused by the binding of ligands. The model predicts that the interaction energy between two ligands decays exponentially with the distance between them and oscillates with the periodicity of the double helix, which by appropriate parameter fitting is shown to quantitatively match with the experimental measurements. Furthermore, the decaying oscillatory trend in the perturbation of groove width in a protein-DNA complex predicted by the model is consistent with the results from molecular simulations.In chapter 2, structural transitions in DNA are studied using ideas from the Zimm-Bragg helix-coil transition theory and the theory of fluctuating elastic rods. Experimental studies on single molecules of DNA have reported several cooperative structural transitions, including the coexistence of three phases, when tensile force or twisting moment is applied to the molecule. The interface energy between two phases of DNA imparts the cooperative character to the force-extension curve or torque-rotation curve observed experimentally. In chapter 5, we choose one such structural transition from dsDNA to single-stranded DNA--called DNA melting--and study it using the statistical mechanics and continuum mechanics of an elastic birod. The detailed microscopic description of the outer-strands and base-pairs admissible in the birod model enables us to decipher why the DNA oligomers with higher GC content are stiffer. Furthermore, a nonlinear asymmetric interaction between the outer strands leads to a sudden and highly cooperative melting transition. Furthermore, the model enables us to examine the effect of tensile force on the melting temperature.

Notes:

Source: Dissertations Abstracts International, Volume: 81-10, Section: B.

Advisors: Purohit, Prashant K.; Committee members: Pedro Castaneda; John Bassani; Yale Goldman.

Department: Mechanical Engineering and Applied Mechanics.

Ph.D. University of Pennsylvania 2020.

Local Notes:

School code: 0175

ISBN:

9798607316976

Access Restriction:

Restricted for use by site license.

This item must not be sold to any third party vendors.