CUBE-DB

CUBE-DB identifies residue-level functional divergence in human and vertebrate protein families by scoring conservation within ortholog groups and divergence between paralogs to highlight sites of functional specialization.

Key Features:

• Nomenclature-Based Organization: Organized using human protein nomenclature to standardize cross-species comparisons.
• Mutual-Best-Hit Strategy: Constructs taxonomically comparable samples for paralogues via mutual-best-hit orthology selection.
• Heterotachy Model: Scores positions based on conservation within a reference ortholog group and divergence from paralogs to identify "functional determinants".
• Homotachy Model: Requires conservation within each paralog group to identify "functional discriminants".
• Phylogeny-Independent Scoring Functions: Employs scoring functions that do not rely on phylogenetic trees and are sensitive to residue type similarity.
• Per-Residue Precomputed Scores: Provides precomputed per-residue scores in tabular form for protein families.
• Structural Mapping: Maps per-residue scores onto related protein structures when structural data are available.

Scientific Applications:

• Evolutionary Biology: Identifies residues underlying functional divergence across vertebrate species.
• Functional Genomics: Supports prediction and annotation of protein function at the residue level.
• Protein Engineering: Informs identification of key residues for designing proteins with altered or novel functionalities.

Methodology:

Analysis uses all available vertebrate genomes, mutual-best-hit orthology to construct comparable paralogue samples, heterotachy and homotachy residue-scoring models, phylogeny-independent residue-type-sensitive scoring functions, and generation of precomputed per-residue scores with optional mapping to structures when structural data exist.