Binding interaction between plasma protein bovine serum albumin and flexible charge transfer fluorophore: A spectroscopic study in combination with molecular docking and molecular dynamics simulation

• Published in: Journal of photochemistry and photobiology. A, Chemistry. Chemistry., 2012-03, Vol.231 (1), p.19-27
• Main Authors: Jana, Sankar, Dalapati, Sasanka, Ghosh, Shalini, Guchhait, Nikhil
• Format: Article
• Language: English
• Subjects: 5-(4-Dimethylamino-phenyl)-penta-2,4-dienenitrile; BSA; FRET; MD simulation; Molecular docking
• ISSN: 1010-6030; 1873-2666
• DOI: 10.1016/j.jphotochem.2011.12.002

[Display omitted] ► Interaction of small fluorophore with plasma protein BSA studied spectroscopically. ► FRET from tryptophan of BSA to probe. ► molecular docking and molecular dynamics simulation complement experimental results. ► Tracking of chemical denaturation of protein by this extrinsic fluorescence probe. Binding interaction of plasma protein bovine serum albumin (BSA) with external flexible charge transfer fluorophore 5-(4-dimethylamino-phenyl)-penta-2,4-dienenitrile (DMAPPDN) has been explored at physiological pH (7.4) by steady state absorption, emission, fluorescence anisotropy, Red Edge Excitation Shift (REES), far-UV circular dichroism (CD), time resolved spectral measurements in combination with molecular docking and molecular dynamics (MD) simulation studies. Chemical denaturation of the protein bound probe by guanidine hydrochloride (GdnHCl) has also been tracked using the spectral response of DMAPPDN. Interaction of the probe with BSA is reflected by the massive blue shift of the fluorophore emission maxima (78nm) with the enhancement of fluorescence intensity due to change of hydrophobic micro-environment of the probe compared to a little change in protein secondary structure. Benesi–Hildebrand plot reveals spontaneous formation of 1:1 BSA–DMAPPDN complex with binding constant 8.821±0.01×103M−1 and binding free energy change −5.359kcalmol−1. Molecular docking study supports the binding of probe in the hydrophobic cavity of sub domain IIA of BSA. The distance for energy transfer from tryptophan of BSA to DMAPPDN measured from fluorescence resonance energy transfer (FRET) results is in good agreement with results of molecular docking study. MD simulation predicts greater stability of BSA–DMAPPDN complex compared to the free protein.