Fiedler Inversion Score (FIS) v3: Calpha-only Spectral Classification of Protein Conformational Transitions -- Expanded Validation n=98

FIS (Fiedler Inversion Score) v3: Expanded validation from n=25 to n=98 protein pairs across 11 functional categories. FIS classifies protein conformational transitions using the cosine angle between Graph Laplacian Fiedler vectors of open and closed states. Parameter-free, computed solely from Calpha coordinates at 8 Angstrom contact cutoff. v3 results (n=98): mean |FIS|=0. 7219, four statistical tests all p<0. 001 (t-test p=1. 35e-8, Wilcoxon p=1. 96e-9, permutation p<0. 0001, Kruskal-Wallis p=4. 24e-5). Three conformational types: Type I domain inversion n=37 (38%), Type II rigidity change n=7 (7%), Type III internal strain n=29 (30%), Mixed n=25 (26%). New finding: 5 additional Type II rigidity proteins beyond EGFR T790M -- FKBP51 (ratio=7. 8x, stress/PTSD target), MMP9 (5. 6x, anti-MMP antibodies), CRBN (4. 3x, lenalidomide/thalidomide molecular glue), Gyrase B (3. 4x, fluoroquinolones), ER-alpha (2. 2x, fulvestrant). All 7 Type II proteins are targets of approved drugs (100% clinical enrichment). Pipeline open-source (fisₚipelineₙ100. py), raw data deposited (FISᵣesultsₙ98. csv). Part of Geometric Systems Medicine series. Companion paper: TRIS (DOI: 10. 5281/zenodo. 20187264). Previous version: FIS v2 (DOI: 10. 5281/zenodo. 20187256).