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Fig. 1. Multivalent binding to protein aggregates. A cross β-sheet fibrillar aggregate presents an organised array of similar binding sites. The binding affinity of monovalent ligands (red) that bind at one site will be low. Divalent ligands (blue) that cooperatively bind at two sites simultaneously can lead to significantly higher binding affinities. The ratio of Kd for the first intermolecular binding interaction (highlighted in red) compared to the effective molarity (EM) for the second intramolecular binding interaction (highlighted in blue) determines the overall increase in binding affinity.