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Epigenetic modifications play diverse roles in biological systems. Nucleic acid modifications control gene expression, protein synthesis, and sensitivity to nucleolytic enzymes. However, the biosynthetic mechanisms of nucleic acid modification can be challenging. Studying protein-ligand interactions helps decipher the regulatory pathways behind biosynthesis and biological responses. Microscale Thermophoresis (MST) can be used to reveal the biomolecular interactions between the phage Mu DNA modifying protein Mom and its ligands. Compared with traditional methods for studying protein-biomolecule interactions, MST requires less sample size, volume, and analysis time, and thus can screen a large number of candidate molecules that interact with proteins of interest. Another notable feature of this method is that it avoids the need for protein purification, which is often a time- and resource-consuming step, and works well with fully or partially purified cell extracts.