Sequence Harmony

Sequence Harmony identifies subfamily-specific functional residues in protein multiple sequence alignments by scoring compositional differences between predefined subfamily groupings using an entropy-based method.

Key Features:

• Entropy-Based Methodology: Uses an entropy-derived formula to assess compositional variations across protein subfamilies and detect subfamily-specific alignment positions.
• Subfamily Grouping Analysis: Operates on multiple sequence alignments with predefined subfamily groupings to select positions that differentiate those groups.
• Intuitive Scoring System: Produces simple, interpretable scores that quantify the degree of compositional difference at each alignment position.
• Integration with Structural Data: Allows predicted subfamily-specific positions to be mapped onto protein structures for spatial analysis.
• Demonstrated on Protein Families: Has identified known functional sites in the receptor-binding domain (MH2) of Smad transcription factors, the Ras-superfamily of small GTPases, and the MIP-family of integral membrane transporters.
• Comparative Performance: In comparisons with AMAS, TreeDet, and SDP-pred, showed superior coverage in selecting known functional sites.

Scientific Applications:

• Functional Site Identification: Detects subfamily-specific positions to elucidate residues underlying functional divergence within protein families.
• Experimental Target Prioritization: Highlights candidate residues for experimental validation of function.
• Structural Mapping and Analysis: Supports examination of how predicted sites cluster or orient within protein models.

Methodology:

Analyzes multiple sequence alignments and computes an entropy-based score of compositional differences between predefined subfamily groupings to identify subfamily-specific positions, with scores that can be mapped onto protein structures.