The hydrophilicity interaction analysis also supports our hypothesis that H3K18Ac cannot interact with N1039 in TRIM33α, as this residue remains oriented away from the BRD pocket during the simulations. We then explored the hydrophobic contacts data from the PLIP analysis in greater detail to identify hydrophobic residues interacting with H3K18Ac (see SI for details). In this analysis, H3K18Ac was found to makes more hydrophobic contacts with F1038 in TRIM33α than F979/F1038 in TRIM24/TRIM33β. This residue directly precedes N1039, and we hypothesize that in TRIM33α this residue can fluctuate to pack against H3K18Ac and helps to stabilize the H3K18Ac-BRD interaction (see SI for details).