Binding affinity and conformational dynamics of globular proteins with surfactants: spectroscopic and computational perspectives.

Abstract

Binding affinity and conformational responses of five cationic surfactants toward three globular proteins (human serum albumin (HSA)/bovine serum albumin (BSA)/ and ovalbumin (OVA)) were studied. Two gemini surfactants - decanediyl-1,10-bis(dimethylhexadecylammonium bromide) (C16-10-C16) and dodecanediyl-1,12-bis(dimethylhexadecylammonium bromide) (C16-12-C16) along with the three monomeric surfactants- cetyltriphenylphosphonium bromide (CTPB), cetyltrimethylammonium bromide (CTAB) and cetylpyridinium bromide (CPB) were employed in the current study. Spectroscopic analysis directed that gemini surfactants exhibited stronger binding and more noteworthy perturbation of the aromatic microenvironment compared with monomeric analogues, with C16-12-C16 steadily revealing the highest binding constant. FTIR measurements exposed substantial shifts in the amide I and II regions, demonstrating a partial alteration of secondary-structure components. These results were supported by DLS observations, which showed that the incorporation of gemini surfactants raises the hydrodynamic diameter, delivering larger protein-surfactant complexes. The experimental outcomes were supported by molecular docking and molecular dynamics simulations, which exhibited that the complex encompassing gemini surfactants had deeper hydrophobic insertion and greater interaction energies. Gemini surfactants, particularly C16-12-C16, have demonstrated improved stability, binding affinity, and structural rearrangement, signifying their possible usefulness as biomolecular modulators for precise drug administration, regulated protein stability, and nanobiotechnological applications. The binding caused substantial conformational changes in the protein's secondary structure, which were principally influenced by polar, hydrophobic, and electrostatic interactions. The gemini surfactants pointed to a higher binding affinity and provoked more significant conformational changes than employed monomeric surfactants.