In silico development of RNA aptamer candidates against thyroid receptor.

Area of Science:

• Biochemistry
• Molecular Biology
• Computational Chemistry

Background:

• Aptamers are short oligonucleotides with high affinity and specificity for molecular targets.
• The conventional method for aptamer selection is Systematic Evolution of Ligands by Exponential Enrichment (SELEX).
• Thyroid hormone receptors (TRs) regulate gene expression and are implicated in metabolic disorders like hyperthyroidism.

Purpose of the Study:

• To develop a non-SELEX, in silico strategy for aptamer discovery.
• To identify RNA aptamers that antagonize nuclear thyroid hormone receptors (TRs).
• To evaluate the potential of identified aptamers as therapeutic agents for hyperthyroidism.

Main Methods:

• In silico simulation of aptamer synthesis and affinity evaluation.
• Knowledge-based retrieval of thyroid hormone response elements (TREs).
• RNA structure prediction, molecular docking, and molecular dynamics simulations.

Main Results:

• Several single-stranded RNA aptamers with strong binding affinity to TRs were identified computationally.
• One candidate aptamer showed a particularly favorable interaction with thyroid hormone receptor alpha.
• The identified aptamers function as potential antagonists by inhibiting TR-TRE interactions.

Conclusions:

• A novel in silico approach successfully identified potential RNA aptamers targeting TRs.
• A lead candidate aptamer demonstrates potential as a therapeutic agent for hyperthyroidism.
• Experimental validation is required to confirm the efficacy of the identified aptamer as a TR-blocking molecule.