OOMMPPAA

OOMMPPAA integrates structural and activity data of protein targets to generate and analyze 3D matched molecular pairs and identify pharmacophoric transformations linked to changes in biological activity.

Key Features:

• Structural and activity integration: Combines protein structural information with activity and inactivity datasets for compound-target pairs.
• 3D matched molecular pairs: Generates 3D matched molecular pairs and produces three-dimensional ligand conformations for paired compounds.
• Pharmacophoric transformation mapping: Identifies pharmacophoric transformations between compound pairs and links those changes to variations in biological activity.
• Binding-site contextualization: Contextualizes activity and inactivity data within protein binding-site environments using 3D structural information.
• Interaction-region identification: Detects critical interaction regions in binding sites associated with specific molecular modifications.

Scientific Applications:

• Lead compound design and optimization: Supports compound design by relating structural modifications to activity changes in a protein-contextualized manner.
• Potency and cell permeability optimization: Demonstrated capability to optimize potency and cell permeability in validation studies.
• Structure–activity relationship (SAR) analysis: Provides insights into nuanced SAR across different compound series.
• Validation on specific targets: Validated on openly available CDK2 datasets and proprietary GlaxoSmithKline data for a SAM-dependent methyl-transferase.

Methodology:

Leverages 3D matched molecular pairs to generate three-dimensional ligand conformations, identifies pharmacophoric transformations between compound pairs and links them to biological activity variations, and contextualizes activity/inactivity data within protein binding-site environments using 3D structural information.