PSI-BLAST (EBI)

PSI-BLAST (EBI) performs iterative protein sequence similarity searches using a position-specific scoring matrix (PSSM) to detect distant homologs and infer evolutionary relationships.

Key Features:

• Iterative Search Process: Performs an initial standard BLAST search to collect significant alignments and iteratively updates a PSSM from those alignments.
• Position-Specific Scoring Matrix (PSSM): Captures residue-specific conservation across aligned sequences to increase sensitivity for weak but biologically relevant similarities.
• Integration of Significant Alignments: Incorporates statistically significant alignments into the PSSM to refine detection of subtle sequence relationships.
• Enhanced Sensitivity and Speed: Uncovers distant evolutionary relationships while maintaining a per-iteration speed comparable to gapped BLAST.
• Detection of Protein Family Members: Enables identification of new members of protein families, exemplified by applications to the BRCT superfamily.

Scientific Applications:

• Distant homolog detection: Identifies remote protein homologs that are not detectable by conventional pairwise BLAST searches.
• Protein function annotation: Aids annotation of unknown proteins by revealing homologs with known functions.
• Protein domain architecture analysis: Assists in characterizing domain composition and conserved residues across related proteins.
• Phylogenetic relationship inference: Supports study of evolutionary relationships among proteins through detection of conserved sequence patterns.
• Protein family discovery: Facilitates discovery and expansion of protein families by detecting weak but significant sequence similarities.

Methodology:

Performs a standard BLAST search, selects statistically significant alignments to construct a position-specific scoring matrix (PSSM), and iteratively searches databases using the evolving PSSM.