o:36088 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 Vezivanje uobičajeno korišćenih antioksidanasa (kvercetin, rezveratrol, i dihidrolipoinska kiselina) za najzastupljenije proteine u cirkulaciji-spektroskopske i in silico i molekulskodinamičke studije simulacije en 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). Antioxidants; proteins; alpha-2-macroglobulin; resveratrol; quercetin; dihydrolipoic acid 1552099 10.1080/07391102.2025.2460087 2025-04-08T12:10:58.365Z 44 yes 46 Miloš Šunderić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka 0000-0002-0940-9481 Vladimir Šukalović Department of Chemistry, University of Belgrade-Institute of Chemistry, Technology, and Metallurgy, National Institute of the Republic of Serbia, Belgrade, Serbia person Ana Penezić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka person 0000-0002-2539-4507 Milan R. Nikolić Department of Biochemistry & Center of Excellence for Molecular Food Sciences, University of Belgrade-Faculty of Chemistry, Belgrade, Serbia person Olgica Nedić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka person 0000-0003-2042-0056 Simeon Minić Department of Biochemistry & Center of Excellence for Molecular Food Sciences, University of Belgrade-Faculty of Chemistry, Belgrade, Serbia person Danilo Četić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia person 0000-0001-9705-3237 Nikola Gligorijević Department of Chemistry, University of Belgrade-Institute of Chemistry, Technology, and Metallurgy, National Institute of the Republic of Serbia, Belgrade, Serbia person application/pdf 96196 https://phaidrabg.bg.ac.rs/o:36088 no yes 18 70 92000001 11A29 11A2905 11A24 11A2404 11A19 11A1903 Journal of Biomolecular Structure and Dynamics Taylor & Francis 2025