Chirobiophore: A Novel Framework for Quantifying Biochirality in Macromolecular Systems.

Area of Science:

• Structural Biology
• Biophysics
• Developmental Biology

Background:

• Chirality is crucial for biological macromolecules but poorly quantified in complex systems.
• Existing stereochemical metrics struggle with distributed and emergent chirality in proteins.

Purpose of the Study:

• Introduce Chirobiophore, a novel paradigm for quantifying biochirality across scales.
• Develop a framework for comparing structurally diverse proteins in a continuous chirality space.
• Bridge the gap between molecular chirality and tissue-level asymmetry.

Main Methods:

• Chirobiophore utilizes a multidimensional, model-independent vector.
• Key descriptors include Local Tetrahedral Asymmetry (LTA), Helical Path Curvature (HPC), Asymmetric Environment Score (AES), Directional Density Profile (DDP), Leaflet Asymmetry Index (LAI), and Orientation Twist Score (OTS).
• The framework enables coordinate-invariant comparisons.

Main Results:

• Demonstrated Chirobiophore application on canonical, GPCR, and complex membrane proteins.
• Revealed distinct chirality signatures and functional clustering within protein families.
• Mapped Chirobiophore descriptors to tissue-level asymmetry indices.

Conclusions:

• Chirobiophore offers a unified and extensible platform for analyzing biochirality.
• Provides new insights into molecular structure, synthetic design, and developmental modeling.
• Enables quantitative assessment of chirality in complex biological systems.