The coarse-grained modelling of HSA with a series of co-solutes has revealed structural and physicochemical features that are highly inuential to the prevention of aggregation via APR shielding. Broadly, ethoxylated compounds had the greatest performance as APR-shielding anti-aggregation agents, and polysorbate species specically were the highest performing class. Branched compounds tended to make greater contact to APRs, particularly those with PEG chains, while phospholipids and fatty acids performed very poorly in shielding APRs from solvent and thereby preventing aggregation. The use of dimensionality reduction coupled with physicochemical descriptors has revealed structural features that are key to optimising protein-excipient interaction. The overall weight of aliphatic chains does not appear to inuence the performance of anti-aggregation agents, provided that some is present.