Fatty acid influence on zinc and uranyl ion binding to human serum albumin: an all atoms molecular dynamics investigation

The potential health risks associated with radionuclides, particularly actinides, have prompted investigations into their interactions with body fluids in living organisms. Human serum albumin (HSA), a plenteous plasma protein with extraordinary binding capacities, is a key player in these interactions. The present study is intended at understanding the interplay between metal ions, namely, zinc and uranyl ions and fatty acids binding with HSA, using all atom equilibrium and non-equilibrium molecular dynamics simulations. Results highlight distinct behaviours of zinc and uranyl ions, elucidating how their interactions with HSA are influenced by the presence of fatty acids. Hydrogen bonding dynamics analysis reveals the disruption of existing bonds due to fatty acid binding, contrasting with the weakening effect caused by metal binding. The resulting conformational changes have significant implications for HSA's structure and dynamics. The potential of mean force (PMF) plots reveals binding and unbinding routes for zinc and uranyl ions, both in fatty acid's presence and absence. Short-range interactions reveal distinct binding behaviours of zinc and uranyl ions, altered by fatty acids, providing insights into unbinding pathways and correlating with the PMF plots.