Bio-GATS

Bio-GATS selects templates for homology modeling of G protein-coupled receptors (GPCRs) by prioritizing hydrophobicity correspondence and structural parameters to improve model relevance for structure-based drug discovery.

Key Features:

• Biophysical hydrophobicity prioritization: Prioritizes hydrophobicity correspondence between target GPCR sequences and potential templates to address low sequence identity among GPCRs.
• Resolution filtering: Considers experimental structure resolution when ranking candidate templates.
• Orthosteric binding pocket similarity: Evaluates similarity of orthosteric binding pocket architecture to favor templates with matching ligand-binding features.
• Structure completeness: Prefers templates with complete structural information.
• Automated template selection: Performs automated selection of appropriate templates for a given GPCR sequence.
• Validation and case study: Validation using recent benchmarking datasets and demonstration on an olfactory receptor case study.

Scientific Applications:

• Homology modeling of GPCRs: Improves selection of structurally relevant templates for building GPCR homology models.
• Structure-based drug discovery: Supports workflows that require accurate GPCR models, relevant given GPCR involvement in physiological functions and as targets of over 30% of FDA-approved drugs.
• Modeling of olfactory receptors: Enables template selection for complex GPCR sequences exemplified by the olfactory receptor case study.

Methodology:

Employs a biophysical approach that prioritizes hydrophobicity correspondence and incorporates parameters including experimental resolution, orthosteric binding pocket similarity, and structure completeness, with automated template selection; validated on recent benchmarking datasets and demonstrated on an olfactory receptor case study.