Abstract
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 (UO22+). A total of six sets of initial coordinates are used for Zn2+-HSA and UO22+-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 UO22+ and Zn2+ 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 UO22+ ion with HSA is the result of the dynamical balance between UO22+-HSA and UO22+-water short range Coulomb interactions. Zn2+ ion interact more strongly than UO22+ at all pH through short range Coulomb interactions. PMF values further concludes that UO22+ cannot associate to the Zn2+ 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
Acknowledgements
Prof(s). A. K. Tyagi is gratefully acknowledged for encouragement during the course of the work. VM is grateful to Dr Pramilla Sawant and Shri Probal Choudhary for their continuous support and encouragement. BARC computer centre is also acknowledged for providing ANUPAM computational facility.
Disclosure statement
The authors declare no conflict of interest.