The interaction between Meropenem drug and human serum albumin (HSA) has been studied under physiological condition in Tris-HCl buffer solution at pH 7.4 by various spectroscopic (UV spectra, fluorescence spectra, CD spectra), Photo-induced HSA cleavage, and molecular docking techniques. The results of fluorescence titration revealed that the Meropenem strongly quench the intrinsic fluorescence of HSA through a static quenching procedure. Binding constants (Kb) and the number of binding sites (n ≍ 1) were calculated using modified Stern-Volmer equations. The thermodynamic parameters ΔG, ΔH and ΔS at different temperatures were calculated which revealed that the electrostatic and hydrogen bonding interactions play a major role in HSA-Meropenem association. The distance r between donor (HSA) and acceptor (Meropenem) was obtained according to fluorescence resonance energy transfer (FRET) and the alterations of HSA secondary structure induced by Meropenem were confirmed by FT-IR and CD measurements. The molecular docking technique was utilized to ascertain the mechanism and mode of action towards the molecular target HSA indicating that Meropenem was located within the subdomain IIA of protein by electrostatic interactions and hydrogen bonds, consistent with the corresponding experimental results. Additionally, Meropenem shows efficient photo-induced HSA cleavage. Our results may provide valuable information to understand the mechanistic pathway of drug delivery and to pharmacological behavior of drug. Research Highlights The interaction of Meropenem with HSA was studied by spectroscopic, photo-induced cleavage and molecular docking techniques. The secondary structure of protein has been changed upon the interaction with Meropenem. Subdomain IIA of the HSA is found to be the main binding site for Meropenem. Communicated by Ramaswamy H. Sarma.
Keywords: Meropenem; human serum albumin; molecular docking.