Cosolvents such as urea, salts and polyols are commonly used in protein processes, yet general understanding of solvent effects on protein-protein interactions is lacking. Although the nature of cosolvent-protein interactions is believed to be weak and non-specific, addition of cosolvent strengthens protein-protein interactions for some proteins, whereas it weakens protein-protein interactions for others. This is exemplified by the puzzling observation made years ago that glycerol increases the binding affinity of one antibody, but decreases the binding affinity of a second antibody to the same antigen. We have analyzed local protein solvation at the binding interface of these antibodies by molecular dynamics simulations and we present two key observations that quantitatively explain the opposing effects of glycerol on the antibody binding affinity. We show that our approach is generally applicable for predicting solvent effects on the affinity of protein-protein complexes for which atomic structures are available.

Predicting solvent effects on antibody binding affinity by scrutinizing solvation at the binding interface

243rd National Meeting (2012)

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