CL5D Hybrid Model for Protein–Ligand Interaction Dynamics

The accurate description of protein–ligand binding dynamics remains a challenge for staticstructural methods such as X-ray crystallography and cryo-EM. Here we introduce theCL5D hybrid model, a deterministic, agent-based framework that integrates entropy (At), fractal geometry (Ab), harmonic progression (Ex), and permutation entropy (T) to computea single Cn score. The Cn score classifies interactions into four phases: Phase I (Excellent/ Good / Moderate / Bad / Very bad), Phase II (Evolution and Decay), Phase III (singularity), and Phase IV (cycle reset). We apply CL5D to 33 BACE1 inhibitors withreported IC50 values (0. 0002–0. 149nM at 2 ◦C). While 32 compounds fall into Phase I, one ligand (Monomer 209917, IC50 = 0. 0002 nM) uniquely enters Phase II (Decay) withCn = 7. 04 × 10^−5. This compound is identified as a Super Dynamic Candidate, predictedto exhibit ultra-fast on/off kinetics, a shallow energy well, and near-perfect pocketentry—potentially involving quantum tunnelling. The CL5D model offers a new lens fordynamic drug design, distinguishing classical reversible binders from rare, super-efficaciousmolecules.