Theseus is a program that simultaneously superimposes multiple macromolecular structures. Instead of using the conventional least-squares criteria, Theseus finds the optimal solution to the superposition problem using the method of maximum likelihood. By downweighting variable regions of the superposition and by correcting for correlations among atoms, the ML superpositioning method produces much more accurate results.

When superpositioning macromolecules with different residue sequences, other programs and algorithms discard residues that are aligned with gaps. Theseus, however, uses a novel maximum likelihood superposition algorithm that includes all of the data.

A conventional least-squares superposition of the Kunitz domain from PDB ID 2sdf is shown at left. A maximum likelihood superposition from Theseus is shown at center. At right is the first principal component of the superposition plotted on the family of models. The red loops at lower right are highly correlated with each other, whereas they are moderately anti-correlated with the light blue strands at left center.