GPCRM

GPCRM predicts three-dimensional structures of G-protein-coupled receptors (GPCRs) to support structural characterization of binding sites, transmembrane domains, and receptor-ligand interactions for biochemical and drug-discovery research.

Key Features:

• Efficient homology modeling: Uses profile-profile alignment and integration of multiple structural templates with Z coordinate-based filtering to refine GPCR models.
• Loop modeling: Implements two loop modeling methods, Modeller and Rosetta, to model flexible regions of GPCRs.
• Scoring functions: Provides Rosetta, Rosetta-MP, and BCL::Score (a membrane-fitted knowledge-based energy function) for model selection focused on binding sites, transmembrane domains, or overall receptor shape.
• Performance: Reduces model generation time from days to hours or minutes while maintaining comparable average model quality.
• Template diversity: Maintains an evolving template database (reported growth from ~20 to over 90 templates) including multiple conformations of the same receptor bound to different ligands.

Scientific Applications:

• Structure-based drug discovery: Supports identification and structural assessment of GPCR binding sites for therapeutic development.
• Receptor-ligand interaction analysis: Enables comparative modeling of ligand-induced conformational changes across GPCR conformations.
• Transmembrane domain characterization: Facilitates modeling and comparison of transmembrane helices and overall receptor topology.

Methodology:

Profile-profile alignment, integration of multiple structural templates, Z coordinate-based filtering, loop modeling with Modeller and Rosetta, and scoring with Rosetta, Rosetta-MP, and BCL::Score.