محمد حسین فاطمی

The interaction of Nilotinib (NIL) with alpha lactalbumin (α-LA) were studied by spectrofluorimetry, UV-Vis spectroscopy, circular dichroism (CD) and molecular modeling methods. Static quenching procedure fluorescence spectroscopy revealed that the fluorescence quenching of α-LA by NIL was the reason of formation of complex) NIL–α-LA. Fluorescence, UV-Vis, and CD spectra of NIL–α-LA complex showed that the conformation of α-LA has been changed in the presence of NIL. Based on the fluorescence quenching analyses the binding constant is calculated which is (467.73 × 104 M–1 at 298 K) and number of ligand-binding site is equal to one then the thermodynamic parameters of this complex are (ΔG = –33.011 kJ mol−1, ΔS = –80.005 J mol−1 K−1; ΔH = −157.70 kJ mol−1) at 298 K which were computed by using van’t Hoff equation and revealed that the reaction between ligand and protein is spontaneous and hydrogen bonding and van der Waals forces played a key role in the binding of NIL to α-LA. The results of molecular docking investigations have good agreement with the results of fluorescence spectroscopy studies. The molecular dynamic simulation (MDS) showed that free α-LA and the NIL–α-LA complex reached equilibration after 20 ns according to monitoring their root mean square deviation (RMSD). Finally, analyzing the root mean square fluctuations (RMSF) show that interaction of NIL with α-LA did not cause a significant conformational change in α-LA during the simulation.