Multi-Harmony

Multi-Harmony identifies sub-type-specific amino acid sites from multiple sequence alignments to reveal residues underlying functional specialization within protein families.

Key Features:

• Integration of Sequence Harmony and multi-Relief: Combines Sequence Harmony (SH) and multi-Relief (mR) algorithms to analyze multiple sequence alignments for specificity-determining positions.
• Sequence Harmony extended: Extends Sequence Harmony to handle more than two sub-groups for analysis across multiple functional sub-families.
• Deterministic multi-Relief: Replaces the original sampling-based multi-Relief with a deterministic implementation to improve consistency of residue prioritization.
• Z-score statistical validation: Both methods produce Z-scores to assess the significance of identified specificity residues.

Scientific Applications:

• Structural biology: Localizing subtype-specific residues to interpret molecular mechanisms of ligand binding and protein–protein interaction differences between sub-families.
• Functional genomics: Identifying residues responsible for functional divergence to guide experimental design and hypothesis testing about protein function.
• Therapeutic targeting: Prioritizing residues and sites as potential targets for development of sub-family-specific drugs.

Methodology:

Starts from a multiple sequence alignment of proteins from the same family with defined sub-groups and applies the extended Sequence Harmony and deterministic multi-Relief algorithms to detect specificity-determining residues and compute Z-scores.