1. Conceptual Breakthrough: Allostery Emerges at Boundaries, Not Cores

Traditional allostery models—rigid‑body rotation, α/β domain shifts, enthalpy/entropy decomposition—fail to explain many experimentally observed allosteric behaviors.

The Boundary‑Centric Allostery (BCA) Model proposes that:

• Allosteric propagation originates at structural boundaries,

• Energy transfer occurs through mass‑scaled vibrational networks,

• Functional outcomes depend on boundary topology, not rigid cores.

This reframes allostery as a network‑level phenomenon, not a domain‑level event.

2. The IE Index: A Unified Quantitative Metric for Allosteric Effect

The IE (Impact–Equilibrium) Index is the first framework that integrates:

(1) Impact Energy

Mass‑scaled vibrational energy injected at the ligand‑binding boundary.

(2) Boundary Network Propagation

Energy flow through a weighted, topology‑dependent boundary network.

(3) Equilibrium Docking Energy

The final energetic state at the functional site.

This index provides a continuous, quantitative measure of allosteric influence— a capability missing from all existing models.

3. Why This Matters Globally

A. Solves the “unmeasurable allostery” problem

For decades, allostery has been described qualitatively. The IE index enables predictive, reproducible quantification.

B. Enables allosteric‑clean drug design

By identifying boundary‑specific propagation paths, the model allows design of molecules that:

• Activate desired pathways

• Avoid off‑target propagation

• Minimize systemic side effects

This is a major unmet need in global pharmaceutical research.

C. Integrates physics, structural biology, and drug design

The model unifies:

• Vibrational physics

• Network theory

• Structural biology

• Computational docking

• Medicinal chemistry

Such integration is rare even in top research institutions.

4. Distinctive Features Compared to Existing Global Models

This positions the BCA/IE framework as a next‑generation allostery theory.

5. Practical Applications

• Predicting allosteric pathways in large proteins

• Designing selective inhibitors with minimal off‑target effects

• Reinterpreting mutational impacts through boundary topology

• Reconstructing allosteric networks from structural data

• Guiding AI‑driven molecular design

The model is compatible with existing computational pipelines and can be integrated into global drug discovery workflows.

6. Why This Framework Is Globally Significant

The BCA/IE theory provides:

• A new conceptual foundation

• A quantitative index

• A mechanism‑driven design principle

• A unified language for physicists, biologists, and chemists

This combination is exceptionally rare. It positions the theory not as incremental progress, but as a paradigm‑level contribution to the field of allostery.