FUGUE

FUGUE recognizes distant homologues through sequence-structure comparison.

Key Features:

• Environment-Specific Substitution Tables: Uses substitution tables tailored to local structural environments of amino acids (secondary structure, solvent accessibility, hydrogen bonding) derived from structural alignments in the HOMSTRAD database.
• Structure-Dependent Gap Penalties with Automatic Alignment Algorithm Selection: Automatically selects between global-local and global alignment algorithms based on sequence–structure length disparity and applies gap penalties that depend on solvent accessibility, relation to secondary structure elements (SSEs), and SSE conservation.
• Integration of Multiple Sequences and Structures: Aligns multiple sequences against multiple structures simultaneously to capture conservation and variation information for more robust homology detection and sequence-structure alignments.

Scientific Applications:

• Distant homologue detection: Identification of remote protein homologues through sequence-structure comparison.
• Structure-based sequence alignment: Generation of sequence-structure alignments that account for local structural context and gap behavior.
• Structural and evolutionary analysis: Comparative analysis of protein relationships and conservation patterns in structural biology and evolutionary studies.

Methodology:

FUGUE employs environment-specific substitution tables derived from HOMSTRAD structural alignments, structure-dependent gap penalties, automatic selection between global-local and global alignment algorithms based on length disparity, and simultaneous alignment of multiple sequences to multiple structures.