To elucidate the structural and energetic basis of attractive protein interactions in the aging lens, we investigated the binding of destabilized mutants of βB1‐crystallin to the lens chaperones, α‐crystallins. We show that the mutations enhance the binding affinity to αA‐ but not αB‐crystallin at physiological temperatures. Complex formation disrupts the dimer interface of βB1‐crystallin consistent with the binding of a monomer. Binding isotherms obtained at increasing concentrations of βB1‐crystallin deviate from a classic binding equilibrium and display cooperative‐like behavior. In the context of βB1‐crystallin unfolding equilibrium, these characteristics are reflective of the concentration‐dependent change in the population of a dimeric intermediate that has low affinity to αA‐crystallin. In the lens, where α‐crystallin binding sites are not regenerated, this may represent an added mechanism to maintain lens transparency.