In Silico Simulation of Aptamer-Tau Interactions for Alzheimer's Disease Therapy

Overview

Alzheimer's disease (AD) is the leading cause of dementia, characterized by the pathological accumulation of amyloid -beta (Aβ) plaques and tau protein aggregates, which disrupt neuronal signaling and lead to cognitive decline. In recent years, aptamers —short, structured oligonucleotides with high affinity and specificity for target biomolecules —have emerged as promising therapeutic agents for neurodegenerative diseases. Recently, bi -specific DNA-based aptamers, which first pass the BBB via transferrin recep tors and later inhibit tau oligomerization, have been developed. I hypothesize that tau proteins contain specific binding sites that enable aptamer interaction, thereby preventing fibril formation. This study focuses on the computational characterization of bi-specific aptamers that facilitate blood -brain barrier (BBB) penetration via transferrin receptors and subsequently inhibit tau oligomerization. The three -dimensional structures of aptamers were generated using the Vfold, incorporating both secondary and tertiary structures. Molecular docking simulations were conducted using HDOCK to analyze aptamer interactions with transferrin receptors and tau proteins. P2Rank further validated the docking results for binding site prediction and electrostatic surface potential (ESP) analysis to assess complementarity and molecular interactions. Lastly, molecular docking results were analyzed using virtual reality (VR) technology. Among the aptamers tested, BW1c exhibited a strong binding affinity to tau protein, suggesting its potential as a first-in-class aptamer-based therapeutic for AD. In addition to computational simulations, I have also designed a novel aptamer analysis pipeline (APTASCAN) that can be used to facilitate future aptamer research. These findings provide a computational framework for designing novel aptamer -based interventions for neurodegenerative disorders.

Competition history

• JSHS 2025 Category not listed

Resources

• National JSHS abstract book ↗

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