Exploring the energetics, binding stability and affinity of Antibiotics with Human Serum Albumin (HSA) in the presence of Acridinedione Dye: Photophysical and theoretical approach

Energetics and bimolecular interactions of Human Serum Albumin (HSA) withantibiotics as the guest molecule and acridinedione (AD) dye as the competing guest, wereinvestigated by molecular docking (MD) methodology. Twenty-three antibiotics were dockingbased on their significance in the field of medicinal chemistry. Among the antibiotics,azithromycin, streptomycin and vancomycin resulted in an unfavourable binding with HSAcompared to all other HSA-antibiotics complex. Interestingly, incorporating AD dye to drugprotein complex resulted in stabilisation as well as destabilisation, based on the nature of theantibiotic. However, docking of drug to AD dye-HSA complex resulted in extensivedestabilisation on the binding affinity of dye towards HSA. The antibiotics predominantlyprefer to reside in 1B, 2A, and 3A subdomains of HSA. However, simultaneous docking of dyeto drug-protein complex displaces the drug to other subdomains such as IA/2B/3B.Interestingly, dye and drug are docked far away from each other in the native protein structurewhen docked simultaneously. Hydrogen-bonding (HB) interaction resulting from the aminoacids of HSA governs the binding stability of antibiotics, whereas both HB and hydrophobicinteractions coexist in drug-protein complex in the presence of AD dye. The study excludingwater molecules provides an efficient approach to ascertain the nature of the bimolecularinteraction existing between host-guest/competing guest assemblies. MD approach providessignificant information on the nature of amino acids involved in bonding accompanied withvarious forces of interaction governing the complex stability.