The capture of uranyl, UO22+, by a recently engineered protein with high selectivity and femtomolar sensitivity has been examined by a combination of density functional theory, molecular dynamics and free-energy simulations. We found that UO22+ is coordinated to five carboxylate oxygen atoms from four amino acid residues of the super uranyl binding protein, (SUP). A network of hydrogen bonds between the amino acid residues coordinated to UO22+ and residues in its second coordination sphere also affects the protein’s uranyl binding affinity. Free-energy simulations show how UO22+ capture is governed by the nature of the amino acid residues in the binding site, the integrity and strength of the second-sphere hydrogen bond network and the number of water molecules in the first coordination sphere. Alteration of any of these three factors through mutations generally results in a reduction of the binding free-energy of UO22+ to the aqueous protein as well as of the difference between the binding free-energies of UO22+ and other ions (Ca2+, Cu2+, Mg2+, and Zn2+), a proxy for the protein’s selectivity over these ions.

Combined theoretical and experimental study of the binding features of the super uranyl-binding protein

249th National Meeting (2015)

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