Elucidating the binding mechanism of an antimigraine agent with a model protein: insights from molecular spectroscopic, calorimetric and computational approaches

Sumatriptan (SUM), a serotonin activator used to treat migraines and cluster headaches. Molecular spectroscopic methods including fluorescence quenching, time dependent fluorescence, FRET, absorption, circular dichroism, differential scanning calorimetric and computational approaches were employed to unravel the interaction between sumatriptan and bovine serum albumin (BSA). The fluorescence quenching studies suggested the interaction between SUM and BSA with a moderate binding with the binding constant (K-b) in the order of 10(4). The findings of temperature and time dependent fluorescence quenching studies confirmed the role of static quenching mechanism. Thermodynamic parameters suggested the key role of electrostatic force in the interaction of SUM with BSA. Absorption and CD spectral studies revealed the bioenvironmental changes around the Trp in BSA upon binding of SUM. Calorimetric based thermal denaturation results confirmed that the thermal stability of BSA was improved in the presence of SUM. resulted in the this decreased flexibility of protein chain. Site competitive studies indicated SUM was located in the hydrophobic cavity of site I which was further confirmed by the docking and dynamic simulation studies. Additionally, molecular dynamics simulations inferred the microenvironmental condition around the SUM and the amino acids and forces involved in the binding of SUM with BSA. Communicated by Ramaswamy H. Sarma