Abstract
The interaction between ketoprofen and bovine serum albumin (BSA) was investigated by molecular simulation, fluorescence and UV-vis spectroscopy methods under the simulated physiological conditions. Molecular simulation method performed to reveal the possible binding mode or mechanism suggested the binding forces between ketoprofen and BSA were mainly hydrophobic interaction and hydrogen bond, which was in agreement with the thermodynamic study (ΔHΦand ΔSΦwere calculated to be 74.514 kJ/mol and 333.98 J/mol · K). The binding constants of ketoprofen and BSA at different temperatures (298, 310 and 318 K) were calculated according to the data obtained from fluorescence spectra and the results indicated that ketoprofen had strong ability to quench the intrinsic fluorescence of BSA via a combination of static and dynamic quenching. Meanwhile, the changes of the conformation of BSA caused by ketoprofen were qualitatively analyzed with the UV-vis and synchronous fluorescence spectroscopy. The distance between ketoprofen and tryptophan residue in BSA was calculated to be 1.58 nm.
Highlights
Studies with protein have received much interest in life sciences, chemistry, and medicine as they showed broad and promising applications in the area of rational drug design [11,14] and facilitated to understand binding mechanism of small molecule drugs and protein
The molecular docking method was used to study the mode of action between bovine serum albumin (BSA) and ketoprofen; the binding constants K and thermodynamic data were obtained at different temperatures by fluorescence spectroscopy; the main binding force was speculated and the distance between BSA and ketoprofen was calculated according to the energy transfer mechanism, which provided referenced experimental data and theoretical basis for discussing the mechanism of non-steroidal anti-inflammatory drugs (NSAIDs) drugs
Molecular simulation: Considering the crystallographic structure of BSA was not included in the Protein Data Base (PDB), the three-dimensional feature of its model was obtained by a homology modeling procedure on the basis of the crystal structure of HSA, which was selected from the complexation of HSA and hemoglobin in PDB (PDB code: 1n5u) [25]
Summary
Studies with protein have received much interest in life sciences, chemistry, and medicine as they showed broad and promising applications in the area of rational drug design [11,14] and facilitated to understand binding mechanism of small molecule drugs and protein. Its anti-inflammatory effect is approximately 160 times of aspirin on a unit weight basis [15] and its pharmacological activity is primarily on the inhibition of cyclooxygenase ( known as cyclooxygenase, COX) created during the metabolism of arachidonic acid and decreases the synthesis of prostaglandins (PGs), thereby acting as a antipyretic, analgesic and anti-inflammatory agent to moderate various pain such as postoperative pain, dental pain, acute visceral pain, acute muscle injury and pain, chronic cancer pain and primary dysmenorrheal In clinical, it is used as an anti-rheumatic drug, commonly used to treat ankylosing spondylitis, rheumatoid arthritis and osteoarthritis. Spectroscopy because of its high sensitivity, rapidity and ease of implementation, has been widely used to investigate drug binding with serum albumins [12,24] Problems such as binding sites of small drug molecules with serum albumins and effects of drugs on conformational changes of serum albumins have not been solved. The molecular docking method was used to study the mode of action between BSA and ketoprofen; the binding constants K and thermodynamic data were obtained at different temperatures by fluorescence spectroscopy; the main binding force was speculated and the distance between BSA and ketoprofen was calculated according to the energy transfer mechanism, which provided referenced experimental data and theoretical basis for discussing the mechanism of NSAID drugs
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