Background: Domains are the basic functional units of proteins. Information on domain- domain interaction is favorable for more detailed understanding of protein-protein interactions, cellular function and biological processes. Molybdopterin containing enzymes are present in a wide range of living systems and have been known for several decades. The enzymes share common structural features, but reveal different polypeptide folding topologies.

Materials and Methods: On the basis of sequence alignments, six families of molybdenum-cofactor-containing enzymes were identified. These conserved structural domains provide clear indications for structural relationships that emerge from these trees and result in groupings that also reflect related functions. Most commonly, this process occurs through comparison of protein sequence profiles or hidden markov models (HMMs). The applicability of these prediction methods by using predicted interaction sites as target binding interfaces were demonstrated.

Results: The results suggest that it is possible to predict domain interaction sites with quite a high accuracy using only sequence information.

Conclusion: The algorithms and analysis presented here significantly improve the ability to identify molybdopterin-binding domain and further advance of the relationship between evolutionary sequence conservation and structure-function attributes of proteins.