FLEXR

FLEXR automates construction of multi-conformer models by applying Ringer-based electron-density sampling to identify and integrate alternate side-chain and backbone conformations in high-resolution crystallographic electron-density maps.

Key Features:

• Automated multi-conformer model building: Constructs explicit multi-conformer models from crystallographic electron-density maps.
• Ringer-based electron-density sampling: Employs Ringer-based sampling to detect alternate conformations and higher-energy density features.
• Alternate-state identification and integration: Identifies hidden alternate states in electron-density maps and integrates them into structural models for refinement, inspection, and deposition.
• Detection of side-chain and backbone heterogeneity: Reveals previously undetected side-chain and backbone conformations, with emphasis on ligand-binding sites.
• Validation on high-resolution datasets: Demonstrated on crystal structures with resolutions between 0.8 and 1.85 Å.
• Addresses PDB underrepresentation: Targets underrepresentation of alternative conformations in Protein Data Bank (PDB) models, where approximately 18% of side chains in high-resolution models exhibit variability.

Scientific Applications:

• Structural model refinement and deposition: Improves completeness of structural models submitted for refinement and deposition by adding explicit alternate conformations.
• Analysis of protein-ligand interactions: Reveals alternate conformations in ligand-binding sites to inform studies of protein-ligand binding mechanisms.
• Ligand discovery and drug design support: Provides structural information on higher-energy and alternate states that can inform ligand discovery and drug design efforts.
• Characterization of conformational heterogeneity: Enables systematic detection of conformational variability in high-resolution crystallographic datasets.

Methodology:

Applies Ringer-based electron-density sampling to crystallographic electron-density maps and builds explicit multi-conformer models by identifying and integrating alternate states into structural models for refinement, inspection, and deposition.