Evaluating the fold of a homology model with homolmapper. [A] Insertion frequency projected onto a homology model. Coproporphyrinogen oxidase (CPO) shares the same overall fold with the ferredoxin-dependent bilin reductase (FDBR) family, despite little sequence similarity . A sequence alignment of PcyA, a cyanobacterial FDBR [46, 49-51], to several members of the CPO family was prepared with CLUSTAL [21, 22] and was used with the 1.58Å crystal structure of human CPO  to build a homology model of PcyA in MODELLER . Insertion frequency in a sequence alignment of some 60 members of the FDBR family was projected onto this model structure with homolmapper and is shown colored from dark blue (no insertions) to red (insertions in 20% of sequences). Strikingly, the model predicts that two insertional hot spots fall within central β-strands (top and bottom strands). [B] Insertion frequency with the same FDBR alignment was projected onto the known crystal structure of PcyA  and is displayed with the same coloring conventions. The central beta sheet does not include such hot spots, demonstrating that such analysis can easily identify problematic regions in homology models for further refinement. Figure prepared with VMD , Stride , and homolmapper.