Exploring the Energetics and Binding Stability of βeta-Lactoglobin(βlg)-Antibiotics Complexes with Competing Guest Molecule

Binding studies of a globular protein, βeta-Lactoglobin (βlg) as the host with select antibiotics (guest) were explored by molecular docking methodology. The energetics of βlg-antibiotics complexes were established from their free energy change (docking score) upon complex formation. The forces governing the relative stability of βlg-guest complex were ascertained from the bimolecular interactions. The drugs employed were based on their inhibiting action on βlg. Amoxicillin (AMX), cycloserine (CYC) metronidazole (MET) prontosil (PRO) and sulfanidazole (SUL) were docked with βlg and their energetics were explored with highly competing guest molecule, dicyanomethylene (DCM) dye. The binding efficiency of βlg-antibiotics complex is as AMX > PRO> SUL > MET > CYC. Interestingly, the docking score of βlg-dye complex was energetically more favoured than drug-protein complex. Moreover, the simultaneous docking of the antibiotics destabilizes the βlg-dye complex resulting in a lesser binding affinity. AMX and PRO drastically destabilises the βlg-dye complex by 85% whereas MET and CYC results in decrease of 60%. However, when dye docked to protein bound to the drugs, an enhancement in the binding stability more than two-fold resulted. On the contrary, this phenomenon was not observed when antibiotics docked to dye-protein complex. The study explores the concept of binding stability of βlg -guest versus βlg-competing guest complexes through docking methods. Further, the role of polar / non-polar amino acids influencing the molecular interactions were analysed and explored in depth.