An Approach to Analyzing and Predicting Force-extension Curves of Nucleic Acids

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Date
2023-07-27
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Publisher
Virginia Tech
Abstract

Single-molecule stretching experiments reveal a distinct plateau region in force-extension curves of nucleic acids such as long double-stranded deoxyribonucleic acids (DNA) and ribonucleic acids (RNA). The dissertation comprises two parts. In the first part, we propose an approach to help analyze polymer force-extension curves that exhibit a distinct plateau region. When coupled to a bead-spring dynamic model, the approach qualitatively reproduces a variety of experimental force-extension curves of long double-stranded (ds) DNA and RNA, including torsionally constrained and unconstrained DNA, and negatively supercoiled DNA. In the plateau region of the force-extension curves, our molecular dynamics simulations show that the polymer separates into a mixture of slightly and highly stretched states without forming macroscopically distinct phases. In the second part, we hypothesize that, depending on the sequence composition, multiple distinct plateau regions can be seen in force-extension curves of long dsDNA fragments under physiological solvent conditions. We explore specific long double-stranded DNA sequences where we expect the phenomenon to occur, and to characterize the distribution of states along the polymer. Our molecular dynamics simulations show that multi-plateau regions are observed in the force-extension curves of specific long double-stranded DNA fragments. The formation of mixed states of slightly and highly stretched DNA, co-existing with macroscopically distinct phases in several segments in the plateau regions, is also predicted.

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Keywords
DNA, RNA, Molecular Dynamics
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