Human serum albumin (HSA) is one of the blood plasma proteins, which plays an important role in the transportation of various natural and pharmaceutical compounds in the body. Cinnamaldehyde is the main component of cinnamon extract which has several medicinal properties. In this study, the conformational changes of HSA in the presence of cinnamaldehyde were investigated by UV–Vis, fluorescence and FT-IR spectroscopic methods and the binding parameters of cinnamaldehyde to HSA were determined. The binding site and driving forces of this interaction were calculated using molecular docking softwares. On the other hand, molecular dynamics simulations were also performed with the GROMACS program package. Using the results of the intrinsic fluorescence spectroscopy data, binding constant of 1.14 × 104 M−1 and number of binding sites 0.883 was obtained. FT-IR measurements have shown that the secondary structure of the protein have been changed by the interaction of cinnamaldehyde with HSA. The free energy of binding (ΔG°) and binding constant (Ka) obtained from the intrinsic fluorescence results were − 5.54 kcal mol−1 and 1.14 × 104 M−1 respectively, which is in good agreement with molecular docking results. On the other hand, the molecular docking calculations showed that cinnamaldehyde binding site is located in the IA subdomain of HSA. Spectroscopy, molecular docking and MD simulations methods showed that the cinnamaldehyde is bound to the HSA protein and hydrogen bonding and hydrophobic forces play the most important role in this interaction. Excellent agreement was found between the experimental and theoretical results.
