Challenges in matching secondary structures in cryo-EM: An exploration

Cryo-electron microscopy is a fast emerging biophysical technique for structural determination of large protein complexes. While more atomic structures are being determined using this technique, it is still challenging to derive atomic structures from density maps produced at medium resolution when no suitable templates are available. A critical step in structure determination is how a protein chain threads through the 3-dimensional density map. A dynamic programming method was previously developed to generate K best matches of secondary structures between the density map and its protein sequence using shortest paths in a related weighted graph. We discuss challenges associated with the creation of the weighted graph and explore heuristic methods to solve the problem of matching secondary structures.