Computationally derived structural insights into Rare Earth selectivity in lanmodulin and its variants.

Area of Science:

• Biochemistry
• Structural Biology
• Computational Chemistry

Background:

• Rare earth element (REE) recovery is crucial and can be advanced by protein-based ligands.
• Lanmodulin (LanM) exhibits high selectivity and affinity for REEs, making it a prime candidate for engineered ligands.

Purpose of the Study:

• To elucidate the thermodynamic and structural basis of REE binding in wild-type LanM and its variants.
• To investigate the role of specific EF-hand residue mutations on LanM's REE binding.
• To explore computational methods for predicting and understanding metal-protein interactions.

Main Methods:

• Protein variant structure prediction and molecular dynamics simulations.
• Analysis of binding motifs and inter-residue interactions.
• Thermodynamic binding measurements (apparent Kd) and computational binding energy scoring.

Main Results:

• Strong agreement between experimental binding affinities and in silico binding energy scores for LanM variants.
• Identification of key amino acids outside the direct binding site that influence REE coordination.
• Demonstration that point mutations can cause long-range structural changes affecting metal ion recognition.

Conclusions:

• LanM variants utilize distinct interactions for REE binding, offering insights into protein engineering for selective metal recovery.
• Computational approaches accurately predict binding affinities and reveal mechanisms of metal-protein recognition.
• Structural perturbations, including altered helicity, correlate with binding events and experimental observations.