TopEnzyme

TopEnzyme provides structural enzyme models to expand structural coverage of enzyme functional space for downstream structural analysis.

Key Features:

• Integration with Major Databases: Models and data are linked with the SWISS-MODEL repository and the AlphaFold Protein Structure Database.
• Model Coverage: The collection contains over 200,000 structural enzyme models representing approximately 60% of known enzyme functions and increasing coverage within Swiss-Prot in the absence of experimental structures.
• Quality Assessment: Model quality was evaluated with TopScore, yielding 9,039 good-quality and 1,297 high-quality structures.
• Comparison with AlphaFold2: Comparative analysis against AlphaFold2 models showed an average TopScore difference of 0.04 in favor of AlphaFold2.
• Novel-target Performance: Both TopModel-generated models and AlphaFold2 were tested on targets absent from their training databases and produced structurally coherent models for novel enzymes.

Scientific Applications:

• Structural Biology: Enables analysis of enzyme mechanisms and structural interpretation of enzyme function using representative models.
• Drug Discovery: Supports identification and structural characterization of enzyme active sites and potential drug targets.
• Protein Engineering: Provides diverse structural templates to inform the design and engineering of enzymes with modified or novel functionalities.

Methodology:

Structural models were generated with TopModel, integrated with data from the SWISS-MODEL repository and the AlphaFold Protein Structure Database, and model quality was assessed and compared using TopScore and AlphaFold2 models.