Šunderić, Miloš Šukalović, Vladimir Penezić, Ana Nikolić, Milan R. Nedić, Olgica Minić, Simeon Četić, Danilo Gligorijević, Nikola info:eu-repo/semantics/article 2025 Antioxidants; proteins; alpha-2-macroglobulin; resveratrol; quercetin; dihydrolipoic acid Journal of Biomolecular Structure and Dynamics Taylor & Francis eng ABSTRACT Poor bioavailability and reduced stability are the main drawbacks to efficiently utilizing many naturally occurring antioxidants, so their binding to circulatory proteins is essential. This work investigated whether major human circulatory proteins, besides albumin, including transferrin, alpha-2-macroglobulin, and fibrinogen, bind widely consumed antioxidants and food supplements, including quercetin, trans-resveratrol, and dihydrolipoic acid, thus filling the gap of detailed pharmacokinetic properties of these food supplements. Detailed examination of the protein structural and functional changes that occur upon ligand binding was analyzed by spectroscopic methods and in silico docking and molecular dynamic simulation studies on the model that consists of the protein/antioxidant pair with the highest affinity constant. It was found that alpha-2-macroglobulin binds trans-resveratrol with the highest affinity (Ka of 4.5 x 104 M−1). http://creativecommons.org/licenses/by-nc-nd/4.0/legalcode https://phaidrabg.bg.ac.rs/o:36088 doi:10.1080/07391102.2025.2460087 application/pdf 96196 bytes Binding of the commonly used antioxidants (quercetin, resveratrol, and dihydrolipoic acid) to major circulating proteins-spectroscopic and in silico docking and molecular dynamic simulation studies