Understanding the structure and conformation of bovine hemoglobin in presence of the drug hydroxyurea: multi-spectroscopic studies supported by docking and molecular dynamics simulation

Binding interaction between the small antitumor drug Hydroxyurea (HU) and Bovine Hemoglobin (BHb) has been explored in details from multi-spectroscopic and computational studies. The formation of ground state complex between BHb and HU has been suggested from the electronic UV-Vis and steady-state fluorescence spectroscopic studies. The quenching in fluorescence of BHb in presence of HU at varied concentrations has been analyzed from the SV plots. Static type of quenching has been suggested from time-resolved fluorescence spectroscopic studies. Binding parameters associated with the BHb-HU complex have also been estimated from the temperature dependent fluorescence spectroscopic studies. Alterations in the micro-environment of the Tyr and Trp residues of BHb in presence of HU have been observed from the synchronous fluorescence measurement. The result obtained from CD spectroscopic measurements signify partial unfolding in the secondary structure of BHb due to binding with HU molecule. The experimental observations are supported by theoretical studies. Molecular docking and molecular dynamics simulations have been performed to investigate the structural stability and compactness of BHb in the binding interaction between BHb and HU. The interaction of BHb with HU is expected to provide fundamental insights towards understanding the therapeutic effectiveness of HU upon interaction with BHb used in chemo-, radio therpeutic procedures and also in the treatment of SCD.