fastSCOP

fastSCOP identifies structural domains and assigns SCOP evolutionary superfamilies to query protein structures using 3D-BLAST and MAMMOTH for rapid and accurate structural classification.

Key Features:

• Rapid identification: fastSCOP uses 3D-BLAST to scan SCOP version 1.71 and compares each query structure against entries with less than 95% sequence identity to quickly identify potential domain matches.
• Top-hit selection: The method retrieves the top 10 hit domains from the 3D-BLAST scan, encompassing hits from different SCOP superfamilies.
• Structural alignment refinement: MAMMOTH aligns the top 10 hit structures to refine domain boundaries and improve classification precision.
• Statistical scoring: 3D-BLAST provides a BLAST-like statistical basis for structural searches to support reliable database querying.
• High classification accuracy: Reported classification accuracy is approximately 98% for 586 query structures with an average execution time of about 5 minutes per structure.
• Scalability: Evaluation on 8,700 unannotated SCOP structures resulted in assignment of 7,311 proteins (9,420 domains) to SCOP superfamilies with an average processing time of 9.6 hours.

Scientific Applications:

• Evolutionary classification: Assigns SCOP superfamilies to infer evolutionary relationships between protein structures.
• Functional annotation: Supports inference of protein function for novel or uncharacterized structures via superfamily assignment.
• Structure-function analysis: Provides domain boundary and superfamily information to inform studies of structure-function relationships.
• Large-scale structural annotation: Enables automated assignment of superfamilies across large structural datasets such as unannotated SCOP entries.

Methodology:

3D-BLAST searches SCOP version 1.71 using a structural alphabet database and a substitution matrix to retrieve top hits, and MAMMOTH performs detailed structural alignments of the top hit structures to refine domain boundaries and assign SCOP superfamilies.