Tuning the lanthanide binding tags for preferential actinide chelation: an all atom molecular dynamics study

Area of Science:

• Biochemistry and Molecular Biophysics
• Radiochemistry and Nuclear Chemistry
• Computational Chemistry and Molecular Modeling

Background:

• The lanthanide binding tag (LBT) is a 17-amino acid peptide with high affinity for lanthanide (Ln³⁺) ions.
• Selective separation of trivalent actinide (An³⁺) ions from lanthanides is crucial for nuclear waste management and remediation.
• Existing LBT peptides show high affinity for Ln³⁺ but lack selectivity for An³⁺ over Ln³⁺.

Purpose of the Study:

• To design mutant peptides derived from LBT with enhanced selectivity for An³⁺ over Ln³⁺ ions.
• To investigate the binding dynamics and affinities of modified LBT peptides with representative An³⁺ (Am³⁺) and Ln³⁺ (Eu³⁺) ions.
• To explore the potential of cysteine substitutions in modulating metal ion binding preferences.

Main Methods:

• Design and synthesis of four LBT mutant peptides: M-LBT (wild-type), M-N103C, M-D105C, and M-N103C-D105C.
• All-atom molecular dynamics (MD) simulations to analyze binding dynamics and affinities.
• Enhanced sampling using well-tempered meta-dynamics (WT-MtD) to calculate converged free energy profiles for metal-binding interactions.

Main Results:

• Mutations altered the peptide's binding pocket coordination environment, increasing selectivity for Am³⁺ over Eu³⁺.
• The wild-type LBT showed an unbinding energy barrier of ~60 kJ mol^-1 for Eu³⁺/Am³⁺.
• The N103C mutant exhibited increased binding strength (>100 kJ mol^-1), D105C showed Am³⁺ preference (~70 kJ mol^-1), and N103C-D105C favored Am³⁺ by >20 kJ mol^-1.

Conclusions:

• The N103C mutant is suitable for general chelation of metal ions.
• The N103C-D105C double mutant demonstrates significant preference for Am³⁺, enabling preferential trivalent actinide separation.
• These engineered peptides offer promising applications as selective chelating agents for actinide binding and separation.