Probing the Dynamic Behavior of the Androgen Receptor in the Presence of Heptyl and Methyl Parabens

Author

• Edgardo De Leon, The University of Texas Rio Grande Valley

Date of Award

5-1-2026

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Evangelia Kotsikorou

Second Advisor

Frank Dean

Abstract

The androgen receptor (AR) mediates physiological signaling from endogenous androgens, a function that can be disrupted by endocrine disruptors with serious reproductive and developmental consequences. Parabens, widely used preservatives, inhibit AR signaling in cell-based assays, with inhibitory potency correlating with alkyl chain length: heptylparaben exhibits stronger antagonism than methylparaben, which shows no effect. We hypothesize this differential potency arises from allosteric modulation at the AR Binding Function 3 (BF-3) site, altering dihydrotestosterone (DHT) binding dynamics. Docking calculations using antagonist-bound AR crystal structures, followed by molecular dynamics simulations, show that methylparaben fails to remain bound at BF-3, whereas heptylparaben maintains stable binding through hydrophobic contacts. Heptylparaben binding disrupts hydrogen bonds stabilizing DHT in the ligand-binding pocket and increases pocket volume. Steered molecular dynamics further demonstrates that DHT unbinding requires less work in the heptylparaben-bound system.

Comments

Copyright 2026 Edgardo De Leon. All Rights Reserved. https://proquest.com/docview/3371254583

Recommended Citation

De Leon, E.(2026). Probing the Dynamic Behavior of the Androgen Receptor in the Presence of Heptyl and Methyl Parabens [Master's thesis, The University of Texas Rio Grande Valley]. ScholarWorks @ UTRGV. https://scholarworks.utrgv.edu/etd/1911