A statistical approach to analyse positional dependencies in protein domains

Motivation: Protein domains are usually identified by conserved regions in the primary amino acid structure. Protein functions are dependent on the 3-dimensional structure and the biochemical properties of the amino acids. 3-Dimensional structures are stabilized by interactions between amino acids which are not adjacent in the primary structure. To preserve the structure, even if certain residues of the sequence are mutated, similar interactions must be possible. This property should be reflected by dependencies between residues of positions taking part in an interaction. We use a statistical approach to identify such positional dependencies in aligned protein sequences of the death domain family and the homeodomain. Results: We identified a 12 amino acid region with high correlations in the death domain and the CARD. Most of known mutations in death domain family members and the homeodomain showed a strong correlation with other positions in the protein. Contact: [email protected]