GenDiS3

GenDiS3 catalogs the genomic distribution of protein domain superfamilies, linking protein sequences to structures to facilitate evolutionary and functional annotation.

Key Features:

• Domain Superfamily Census: Identifies sequence homologs for 2060 superfamilies from SCOPe (Structural Classification of Proteins extended).
• Homology Detection: Employs DELTA-BLAST (domain enhanced lookup time accelerated BLAST) for initial detection of hits.
• Domain Validation: Uses HMMSCAN for validation of identified domain hits.
• Homolog Statistics: Identifies over 151 million sequence homologs, with 116 million validated as true positives.
• Case Study Analysis: Enables exploration of domain architecture variations in glycolysis-related enzymes and mutation analysis across evolutionary lineages for genes such as LOG.

Scientific Applications:

• Evolutionary Studies: Supports analysis of domain architecture variations and evolutionary changes in essential proteins.
• Functional Annotation: Facilitates classification and annotation of protein sequences before structures are determined or functions characterized.
• Structural Biology: Bridges the gap between sequence information and 3D structural data by linking distant homologs to known structures.
• Mutation Analysis: Enables identification of significant mutations across evolutionary lineages for specific genes.

Methodology:

GenDiS3 employs a one-time computational exercise to search for trusted homologs of protein domains of known structures against the sequence database using DELTA-BLAST for initial hit detection followed by HMMSCAN for validation.