To gain molecular-scale insight into the protein interactions that stabilize concentrated solutions of wild-type gamma-crystallins and lead to the formation of aggregates in solutions of their cataract-related mutants, the Tobias and Martin labs are conducting a collaborative effort that employs a multi-scale computational modeling approach that is validated and refined using experimental data, including solution and solid-state NMR, light scattering, and small angle x-ray and neutron scattering. Protein configurations from prolonged molecular dynamics simulations in explicit solvent are used to model protein solutions at physiologically relevant concentrations using implicit-solvent Monte Carlo simulations. The resulting multi-protein configurations are further refined using all-atom molecular dynamics simulations. The same approach will be applied to elucidate the molecular-scale details of the interactions of wild-type and cataract-related variants of gamma-crystallins with alphaB-crystallin.