GPCRchimeraDB

GPCRchimeraDB catalogs chimeric and natural G protein-coupled receptors (GPCRs) to facilitate rational chimera engineering, enabling insights into poorly characterized receptors and advancing GPCR therapeutic development.

Key Features:

• Chimeric GPCR Repository: Catalogs 212 chimeric receptors identified through literature review, enabling connections between chimeras and their parent receptors and facilitating exploration of novel parent combinations.
• Natural GPCR Collection: Includes 1,755 class A natural GPCRs with expanded descriptions compared to existing databases by incorporating biophysical profiles.
• Multi-level Annotations: Provides extensive descriptions at the sequence, structural, and biophysical level with annotations from UniProt and GPCRdb and predictions from AlphaFold2 and b2btools.
• Sequence-Structure Visualization: Integrates an interactive sequence-structure (1D-3D) visualization tool to maintain overview of large datasets.
• GPCR Sequence Aligner: Offers a sequence alignment tool demonstrated to outperform current state-of-the-art tools for non-conventional GPCRs.
• Feature Comparator: Enables investigation of differences between natural and chimeric receptors.
• Design Guidelines: Provides guidelines to support rational chimera engineering.

Scientific Applications:

• Signaling Pathway Elucidation: Supports the design of novel chimeric GPCRs to unravel signaling pathways of poorly characterized receptors.
• Structural Characterization: Facilitates identification of key regions and resolution of structures for poorly understood GPCRs.
• Ligand Discovery: Assists in discovering novel ligands of poorly characterized GPCRs through knowledge transfer from well-characterized parent receptors.
• Drug Discovery: Contributes to advances in GPCR therapeutic development by optimizing the design of new chimeras.

Methodology:

Chimeric GPCRs are obtained by merging a well- and less-well-characterized GPCR at the intracellular limits of their transmembrane regions or intracellular loops. The database was constructed through literature review to identify chimeric receptors. Predictions are generated using AlphaFold2 and b2btools.