o:25892 Physicochemical characterisation of dihydro-alpha-lipoic acid interaction with human serum albumin by multi-spectroscopic and molecular modelling approaches Fizičko-hemijska karakterizacija interakcije dihidro-lipoinske kiseline i albumina iz seruma ljudi primenom multi-spektroskopskih metoda i molekulskog modelovanja en ABSTRACT The binding of a popular food supplement and well-known antioxidant, dihydro-alpha-lipoic acid (DHLA) to human serum albumin (HSA) was characterised. The binding was monitored by several spectroscopic methods together with the molecular docking approach. HSA was able to bind DHLA with moderate affinity, 1.00±0.05×104 M-1. Spectroscopic data demonstrated that the preferential binding site for DHLA on HSA is IIA (Sudlow I). Both experimental and molecular docking analysis identified electrostatic (salt bridges) and hydrogen bonds as the key interactions involved in DHLA binding to HSA. Molecular docking confirmed that the Sudlow I site could accommodate DHLA and that the ligand is bound to the protein in a specific conformation. The molecular dynamic simulation showed that the formed complex is stable. Binding of DHLA does not affect the structure of the protein, but it thermally stabilises HSA. Bound DHLA had no effect on the susceptibility of HSA to trypsin digestion. Since DHLA is a commonly used food supplement, knowledge of its pharmacokinetics and pharmacodynamic properties in an organism is very important. This study further expands it by providing a detailed analysis of its interaction with HSA, the primary drug transporter in the circulation. spectral analysis, molecular docking, protein-ligand interaction, protein stability, protein structure 1552099 10.2298/JSC210420041G 2022-06-03T10:02:08.828Z 44 yes 46 Nikola Gligorijević University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka 0000-0002-8691-2486 Ana Penezić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka person 0000-0002-2539-4507 Olgica Nedić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka person 0000-0003-2042-0056 Goran Miljuš University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor biohemijskih nauka person 0000-0001-6417-8711 Simeon Minić University of Belgrade, Faculty of Chemistry, Department of Biochemistry and Center of Excellence for Molecular Food Sciences, Serbia person Vladimir Šukalović University of Belgrade, Institute of Chemistry, Technology and Metallurgy, Serbia person application/pdf 3633556 https://phaidrabg.bg.ac.rs/o:25892 no yes 16 70 92000001 11A29 11A2905 11A24 11A19 11A1903 Journal of the Serbian Chemical Society 86 9 795 807 Srpsko hemijsko društvo 2021