A combined spectroscopic, docking and molecular dynamics simulation approach to probing binding of a Schiff base complex to human serum albumin

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Vol. 103; pp. 11 - 17
• Main Authors: Fani, N., Bordbar, A.K., Ghayeb, Y.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.02.2013
• Subjects: Absorption spectroscopy; Binding Sites; Fluorescence quenching; Human serum albumin; Humans; Molecular docking; Molecular Docking Simulation; Molecular Dynamics Simulation; Protein Binding; Protein Conformation; Schiff base complex; Schiff Bases - chemistry; Schiff Bases - metabolism; Serum Albumin - chemistry; Serum Albumin - metabolism; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - metabolism; Absorption spectroscopy; Human serum albumin; Molecular dynamics simulation; Schiff base complex; Molecular docking; Fluorescence quenching
• ISSN: 1386-1425; 1873-3557
• DOI: 10.1016/j.saa.2012.11.003

[Display omitted] ► The fluorescence of HSA quenched due to interacting with Schiff base complex. ► This compound bound to HSA with high affinity. ► Hydrogen bond played a major role in the binding interaction. ► Schiff base complex was situated within subdomain IB in site 3 of HSA. ► Schiff base complex can interact with HSA, without affecting the secondary structure. The molecular mechanism of a Schiff base complex ((E)-((E)-2-(3-((E)-((E)-3(mercapto (methylthio) methylene)cyclopentylidene) amino) propylimino) cyclopentylidene) (methylthio) methanethiol) binding to Human Serum Albumin (HSA) was investigated by fluorescence quenching, absorption spectroscopy, molecular docking and molecular dynamics (MD) simulation procedures. The fluorescence emission of HSA was quenched by this Schiff base complex that has been analyzed for estimation of binding parameters. The titration of Schiff base solution by various amount of HSA was also followed by UV–Vis absorption spectroscopy and the corresponding data were analyzed by suitable models. The results revealed that this Schiff base has an ability to bind strongly to HSA and formed 1:1 complex. Energy transfer mechanism of quenching was discussed and the value of 5.45±0.06nm was calculated as the mean distance between the bound complex and the Trp residue. This is implying the high possibility of energy transfer from HSA to this Schiff base complex. Molecular docking results indicated that the main active binding site for this Schiff base complex is site III in subdomain IB. Moreover, MD simulation results suggested that this Schiff base complex can interact with HSA, without affecting the secondary structure of HSA but probably with a slight modification of its tertiary structure. MD simulations, molecular docking and experimental data reciprocally supported each other.