Sketching microprotein portraits

The illustrations of intricate molecular machineries inside cells created by David Goodsell continue to inspire the scientific community. Here, we aim to extend his artworks to include microproteins, a newly recognized class of small proteins with less than 100 amino acids, encoded by small open reading frames. Given the rapidly expanding number of identified microproteins, potentially exceeding the number of canonical proteins, we highlight, in this perspective article, diverse computational approaches to classify these proteins. By predicting localization, assessing structural homology, and modeling environments and dynamics of microproteins, these methods could provide clues about the subcellular localization of these microproteins and their structural domain homology, guiding further investigation into their biological functions in living systems.