Date

12-18-2025

Document Type

Thesis

Abstract

Netropsin is a small molecule that binds to the minor groove of DNA and serves as a model scaffold for DNA-minor groove binding anticancer drugs. Understanding how Netropsin interacts with DNA under mechanical stress is important for characterizing how similar molecules function in biological environments. In this work, we used dual-beam optical tweezers to study how Netropsin binding affects the mechanical behavior of single DNA molecules under applied force. Individual DNA molecules were held under controlled forces while Netropsin was introduced at varying concentrations. Constant-force measurements were used to probe binding dynamics; however, we found binding occurred too rapidly to allow reliable extraction of binding and unbinding rate constants. Instead, these measurements consistently reached well-defined equilibrium DNA extensions. To directly examine equilibrium behavior, slow stretching experiments were performed with sufficiently long delay times to ensure equilibrium was maintained at each applied force. Across the force range studied, increasing Netropsin concentration produced systematic increases in DNA extension, indicating force-dependent binding. Equilibrium extensions measured during slow stretching were quantitatively consistent with those obtained from constant-force experiments. This work establishes a foundation for future studies aimed at quantitatively extracting molecular parameters and improving the biophysical understanding of minor-groove binding scaffolds relevant to anticancer drug development.

Department

Physics

Thesis Committee

Dr. Thayaparan Paramanathan, Thesis Advisor
Dr. Edward Deveney, Commitee Member
Dr. Alexandra Zilz, Committee Member

Copyright and Permissions

Original document was submitted as an Honors Program requirement. Copyright is held by the author.

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