CL5D Phase-Dynamic Analysis of Neurodegenerative and Motor Neuron Disease Proteins: α-synuclein (Parkinson's) and Spastin (Hereditary Spastic Paraplegia) Beyond AlphaFold pLDDT

The CL5D Hybrid Model (Papers 1–10, Chakraborty 2026) provides phase-dynamicclassification via the Cn score (Phase I scale: 1 → 0.000123; Benchmark BS = 0.00002,fixed). Paper 10 demonstrated four propositions beyond AlphaFold pLDDT using BACE1(Alzheimer) and MAO-B (Parkinson) as proof-of-concept. This paper extends the samefour propositions to two additional neurodegenerative and motor neuron disease proteinsunder the genomics domain protocol (no 50% gate): α-synuclein (UniProt P37840,Parkinson’s disease, PDB 1XQ8/8A9L) and Spastin (UniProt Q9UBP0, HereditarySpastic Paraplegia SPG4, PDB 6PEN).The CL5D pipeline (At→Ab→Ex→T→Cn) yields Cn = 0.036403 (Excellent) forα-synuclein and Cn = 0.144704 (Excellent) for Spastin, compared to Cn = 0.014417–0.017612 for Paper 10 proteins. The higher Cn values reflect the greater structuralheterogeneity: overfitting percentages reach 76.06% (α-synuclein) and 71.27% (Spastin),significantly above the 39–45% of BACE1 and MAO-B.Four propositions are established: (P1) CL5D Cn trajectories predict phase transitionsthat pLDDT cannot; (P2) the NAC region of α-synuclein (Cn = 0.346, Good) andthe AAA ATPase domain of Spastin (Cn = 0.126, Excellent) show distinct functionalreadiness; (P3) oligomeric state classification via the Ψ(n) = W × Ct selection rulecorrectly distinguishes the α-synuclein monomer from the Spastin hexamer (n∗ = 6);and (P4) per-region Cn scores identify the functional role of disordered regions beyondpLDDT location information. A cross-paper comparison spanning Papers 10–11establishes a Cn signature spectrum for four neurological disease proteins.