The protein-ligand binding in the development of hypersensitivity to folic acid and its analogs

What is it about?

Folic acid plays a vital role in various metabolic processes, including DNA synthesis and repair, cell division, the production of red blood cells, and fetal development. However, hypersensitivity to folic acid and its analogs can occur, leading to various symptomatic manifestations, including shortness of breath, skin rashes, itching, hives, swelling, gastrointestinal disturbances, tachycardia, and anaphylaxis. The mechanism of hypersensitivity to folic acid and its analogs is not well understood. Human serum albumin serves as the primary protein component and plays a crucial role as a carrier for a variety of endogenous and exogenous compounds, including vitamins. Due to the conformational flexibility of human serum albumin, characteristics such as the binding energy, binding site location, and binding orientation of different ligands can vary. As a result, this variability can subsequently influence the immune response. Therefore, studying the complexation of folic acid and its analogs with human serum albumin is of interest to predict the impact of these interactions on the binding of epitopes from these antigens (the complex of human serum albumin with the ligands) to the active sites of IgE antibodies or immune cells receptors. The molecular docking methods were used to predict energetically favorable conformations and the orientations of ligands within the binding site of the protein as well as to assess the binding affinity at the molecular level.

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Photo by National Cancer Institute on Unsplash

Photo by National Cancer Institute on Unsplash

Why is it important?

We performed molecular docking for four ligands that have the potential to act as triggers for hypersensitivity. The involvement of amino acid residues in ligand binding varies across subdomains of human serum albumin. Subdomain IIA and subdomain IB play a significant role in ligand binding through hydrogen bonds and hydrophobic interactions, particularly for folic acid, tetrahydrofolic acid, and 5-methyltetrahydrofolic acid. Subdomain IIIA predominantly binds methotrexate.

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