How are functional residues predicted?
Functional residues are predicted using the INTREPID algorithm, which estimates the degree of evolutionary conservation for each residue in the query sequence. Evolutionary conservation is estimated by retrieving homologous sequences from the UniProt database, aligning these to the query sequence, and inferring a protein family tree. Patterns of conservation across the protein family are then used to estimate the degree of conservation at each position in the sequence. The conservation score reported by INTREPID for each residue is a z-score. This score compares the observed conservation at residue i to the mean conservation across all sites in the sequence, and is the number of standard deviations away from the mean value. Larger positive values indicate highly conserved positions, relative to the rest of the sequence. Large negative values indicate positions that are less conserved than average. For more details on the INTREPID algorithm, please see ( Sankararaman and Sjölander, Bioi
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