Tuning the Lanthanide Binding Tags for Preferential Actinide Chelation: an all atom Molecular Dynamics study

Abstract

The present study focuses on designing mutant peptides derived from the Lanthanide Binding Tag (LBT) to enhance selectivity for trivalent actinide (An³⁺) ions over lanthanides (Ln³⁺) metal ions (M). LBT, a short peptide known for its high affinity towards Ln³⁺, was modified by substituting hard-donor ligands like asparagine (Asn or N) and aspartic acid (Asp or D) with softer ligand cysteine (Cys or C) to create four mutant peptides: M-LBT (wild-type), M-N103C, M-D105C, and M-N103C-D105C. Molecular dynamics (MD) simulations were employed to analyze the binding dynamics and affinities of these mutants with Eu³⁺ and Am³⁺ as representatives for Ln and An ions, respectively. The study utilized enhance sampling method, namely, well-tempered meta-dynamics (WT-MtD) to overcome sampling challenges and obtain converged free energy profiles for the metal-binding interactions. Our simulations studies indicate that both single and double mutations alter the coordination environment within the peptide's binding pocket, potentially increasing Am3+ selectivity over Eu3+ ion. These insights contribute to the developmentofmore effective and selective chelating agents for the preferential actinide binding.