Multifaceted analysis of bempedoic acid binding to subdomain IIA of human serum albumin
Document Type
Article
Publication Date
2-1-2025
Abstract
The molecular association between bempedoic acid (BAC) and the major blood plasma transporter, human serum albumin (HSA), was investigated using molecular docking, molecular dynamics (MD) simulation, isothermal titration calorimetry (ITC), atomic force microscopy (AFM), and spectroscopic techniques. During the docking and MD simulation investigations, it was observed that BAC interacted with subdomain IIA (Site I) of HSA through hydrogen bonds and hydrophobic interactions. This interaction ensured the stability of the complex throughout the duration of 100 ns. The observed enhancement in the fluorescence intensity of HSA after BAC inclusion and the swelling of HSA generated by BAC in the AFM data also suggested the formation of a complex between BAC and HSA. The BAC demonstrated a moderate affinity towards HSA, with a binding constant (K-a) of 1.21 +/- 0.05 x 10(5) M-1 at 300 K. Notable modifications in the secondary and tertiary structures of the protein, as well as changes in the protein's Tyr/Trp surroundings, were observed using circular dichroism and threedimensional fluorescence spectra when the protein was attached to BAC. Insightful information regarding molecular interactions that regulate the stability of the BAC-HSA complex is provided by these investigations.
Keywords
Bempedoic acid, Human serum albumin, Molecular docking, MD simulation, Calorimetry, Microscopy, Human health
Divisions
oralcraniofacial,InstituteofBiologicalSciences
Funders
UCSI University REIG (REIG-FPS-2023/039)
Publication Title
Journal of Molecular Structure
Volume
1322
Issue
2
Publisher
Elsevier
Publisher Location
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS