PSI

PSI performs multiple sequence alignment (MSA) of proteins by combining homology extension with a consistency-based alignment approach and providing transmembrane topology prediction.

Key Features:

• Homology extension (PSI-BLAST): Extends alignments by retrieving homologous sequences using Position Specific Iterated (PSI) BLAST searches across selected databases.
• Reduced-complexity and non-redundant databases: Supports use of reduced complexity and non-redundant sequence databases to accelerate and broaden homology extension.
• Transmembrane protein reference databases: Provides specialized reference databases tailored for transmembrane proteins (TMPs) to improve TMP-specific homology searches.
• Consistency-based alignment: Uses a consistency-based algorithm (TM-Coffee approach) to integrate information from multiple pairwise comparisons and improve MSA accuracy.
• Topological prediction (HMMTOP): Produces transmembrane topology predictions for TMPs using the HMMTOP algorithm.

Scientific Applications:

• Protein sequence analysis: Produces MSAs suitable for comparative sequence analysis and annotation of protein families.
• Structural biology: Generates alignments and TMP topology predictions to inform structural modeling and interpretation.
• Functional genomics: Assists in identifying conserved motifs and functional residues across homologous proteins.
• Membrane protein studies and drug discovery: Enables focused analysis of transmembrane proteins relevant to membrane biology and pharmacology.

Methodology:

PSI-BLAST searches for homology extension across redundant and non-redundant (including reduced-complexity) databases; consistency-based alignment using the TM-Coffee approach; and transmembrane topology prediction using HMMTOP.