Figure 3

Examples where global protein similarity is not adequate to predict function. Shown are the experimental, predicted, and template structures for protein targets Pseudomonas aldolase (PDB identifier 1nvm-A) and Methanococcus phosphosulfolactate synthase (PDB identifier 1qwg-A) colored by the direction of the chain (blue to red). In both cases, the template and predicted structures have the correctly assigned fold but incorrectly assigned function based on similarity. The predicted structures resemble the template structures overall, but some local features (orientation of the second helix in upper panel and an extra helix-like region in lower panel, shown as black boxes in figure) are more similar to what is observed in the experimental structures. Since the FSSA algorithm uses both local sequence and structure information to determine function, it is less susceptible to such biases in global structure when classifying protein function.