GANGSTA+ aligns protein structures hierarchically in three stages starting with an alignment of secondary structure elements (SSE) (first stage), where only alpha-helices and beta-strands are considered as SSEs. Thus, non-sequential structure alignment is facilitated, since loops and coils connecting the SSEs are ignored. GANGSTA+ uses a combinatorial approach to optimize the SSE assignment. For the highest ranked SSE assignments preliminary alignments on the residue level are performed (second stage) using energy minimization with attractive soft interactions between C-alpha atoms pairs belonging to different proteins of the considered pair. In stage three the C-alpha atoms of both proteins are assigned to points of the same three-dimensional grid using the preliminary information of the structural overlay from the second stage. C-alpha atoms belonging to different proteins found at the same or neighbour grid points are assigned again pair-wise to obtain a more accurate and complete SSE assignment. Finally the assignment on the residue level is repeated aligning now also residues, which belong to loops and coils, if possible.