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Despite advancements in understanding protein\u2013crowder interactions, predicting their precise effects on protein structure and function remains challenging. Here, we elucidate the effects of PEG\u2010induced crowding on the fluorescent protein mCherry using molecular dynamics simulations and fluorescence\u2010based experiments. We identify and characterize specific PEG\u2010induced structural and dynamical changes in mCherry. Importantly, we find interactions in which PEG molecules wrap around specific surface\u2010exposed residues in a binding mode previously observed in protein crystal structures. Fluorescence correlation spectroscopy experiments capture PEG\u2010induced changes, including aggregation, suggesting a potential role for the specific PEG\u2013mCherry interactions identified in simulations. Additionally, mCherry fluorescence lifetimes are influenced by PEG and not by the bulkier crowder dextran or by another linear polymer, polyvinyl alcohol, highlighting the importance of crowder\u2013protein soft interactions. 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