QM Investigation of Rare Earth Ion Interactions with First Hydration Shell Waters and Protein-Based Coordination...

Area of Science:

• Computational Chemistry and Biochemistry
• Bioinorganic Chemistry
• Materials Science

Background:

• Conventional rare earth metal (REM) extraction is inefficient, costly, and environmentally harmful.
• Lanmodulin (LanM) protein shows high affinity and selectivity for REMs, inspiring novel refinement strategies.
• Understanding REM interactions with biological molecules is crucial for developing new separation technologies.

Purpose of the Study:

• To investigate trivalent lanthanide cation (Ln³⁺) interactions with water and protein binding sites using quantum mechanical (QM) methods.
• To compare computational predictions with experimental data for LanM and a lanthanum-binding peptide (7CCO).
• To explore the potential of computational approaches for designing efficient REM-binding peptides.

Main Methods:

• Employed quantum mechanical (QM) methods, including energy decomposition analysis (EDA), to study Ln³⁺ interactions.
• Utilized quasi-chemical theory (QCT) to calculate relative binding free energies, incorporating explicit first hydration shell waters.
• Modeled bulk solvent effects using an implicit continuum model and compared results with PDB structures (7CCO and LanM).

Main Results:

• EDA revealed distinct energetic contributions of Ln³⁺ interactions with water versus protein binding sites, emphasizing electrostatics and polarization.
• Calculated binding affinities generally increased down the periodic series for both water and protein models, with a slight exception for Lu³⁺.
• The truncated 7CCO model successfully reproduced experimental Ln³⁺ relative binding free energies, validating the computational approach.

Conclusions:

• QM modeling provides valuable insights into Ln³⁺ interactions with biomolecules and bioinspired systems.
• The study demonstrates an effective computational platform for designing specific, single-site REM-binding peptides more efficiently.
• Discrepancies with LanM experimental data suggest the need for models incorporating longer-range interactions and cooperative effects.