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Antibody fragments are emerging as promising therapeutics, with biomolecular recognition properties on par with full-length monoclonal antibodies, while also providing advantages in terms of biodistribution and manufacturability. While antigen-binding fragments are generally easy to produce, with a variety of expression systems available, the downstream processing has faced challenges due to the lack of a mild selective capture approach for purification. This study addresses the challenge by demonstrating that directed evolution of a Protein G-derived antibody-binding domain into a calcium-dependent ligand, C2_{Ca EP7}, that enables mild capture and elution of full-length mouse IgG1 by the interaction with the Fab-fragment. The evolved ligand allows efficient purification of mouse IgG1 with calcium-triggered elution at neutral pH, eliminating the need for acidic conditions typically used in affinity chromatography. Optimization studies demonstrate that while the monomeric format elutes antibodies at moderate salt concentrations, a tetrameric configuration enhances binding strength (in 1 mM CaCl₂) through avidity effects and enables near-complete antibody recovery without leakage using 150 mM NaCl and 100 mM citrate for elution. Mechanistically, solution-state NMR reveals that a unique E35G scaffold mutation, acting synergistically with loop modifications, destabilizes the domain in the absence of calcium, leading to loss of tertiary structure and disruption of the antibody-binding interface, while calcium binding restores the native conformation and functional binding surface. Collectively, these results establish a calcium-switchable affinity system that enables robust, mild, and scalable antibody purification at neutral pH without residual product remaining on the column.