Binding of human serum albumin with uranyl ion at various pH: an all atom molecular dynamics study.

Uranium is routinely handled in various stages of nuclear fuel cycle and its association with human serum albumin (HSA) has been reported in literature, however, their binding characteristics still remains obscure. The present study aims to understand interaction of uranium with HSA by employing all atom molecular dynamics simulation of the HSA-metal ion complex. His67, His247 and Asp249 residues constitute the major binding site of HSA, which capture the uranyl ion (UO 2 2+ ). A total of six sets of initial coordinates are used for Zn 2+ -HSA and UO 2 2+ -HSA system at pH = 4, 7.4 and 9, respectively. Enhance sampling method, namely, well-tempered meta-dynamics (WT-MtD) is employed to study the binding and un-binding processes of UO 2 2+ and Zn 2+ ions. Potential of mean force (PMF) profiles are generated for all the six sets of complexes from the converged WT-MtD run. Various basins and barriers are observed along the (un)binding pathways. Hydrogen bond dynamics and short-range Coulomb interactions are evaluated from the equilibrium run at each basins and barriers for both the ions at all pH values. The binding of UO 2 2+ ion with HSA is the result of the dynamical balance between UO 2 2+ -HSA and UO 2 2+ -water short range Coulomb interactions. Zn 2+ ion interact more strongly than UO 2 2+ at all pH through short range Coulomb interactions. PMF values further concludes that UO 2 2+ cannot associate to the Zn 2+ bound HSA protein but can be captured by free HSA at all pH values i.e. endosomal, alkaline and physiological pH.Communicated by Ramaswamy H. Sarma.