Abstract—In this work binding properties and conformational changes in alpha lactalbumin ( α -LA) upon interaction with sorafenib were investigated by spectrofluorimetry, UV-Vis spectroscopy, Fourier transform infra- red spectroscopy and molecular modeling methods. The fluorescence spectroscopic results revealed that sorafenib could effectively quench the intrinsic fluorescence of alpha lactalbumin through a static quenching mechanism. Evaluation of the thermodynamic parameters ( ΔH0 = –120.167 kJ mol–1 , ΔS0 = –309.507 J mol–1 K–1 ) suggested that the binding process was spontaneous while hydrogen bonds and van der Waals forces played a major role in this interaction. The fluorescence, UV-absorption and FT-IR spectra showed that conformational changes occurred in alpha lactalbumin structure after interaction with sorafenib. The molecular docking studies showed one binding site in alpha lactalbumin which most of its interactions are hydrophobic. The value of calculated docking ΔG0 (–27.11232 kJ mol–1 ) (is in agreement with those obtained from fluorescence spec- troscopy measurement. Finally, molecular dynamics simulation was performed on the best docked complex by considering the permanence and flexibility of α -LA–sorafenib complex in the binding site.
