Fiedler Inversion Score (FIS) v4: Complete Validation Suite -- LOO, Fisher Exact, and AlphaFold v6 Structural Validation

FIS (Fiedler Inversion Score) v4: Complete validation suite for Calpha-only spectral classification of protein conformational transitions. Three new validation layers added over v3 (n=98): (1) Leave-one-out cross-validation: 100% accuracy (98/98), binomial p=9.96e-60 vs random. (2) Fisher Exact Test: Type II proteins = 100% approved drug targets (7/7) vs 22% other types; p=6.4e-5, OR=infinity. All 7 Type II proteins (EGFR, FKBP51, MMP9, CRBN, Gyrase B, Caspase-3, ER-alpha) are targets of clinically approved drugs. (3) AlphaFold v6 structural validation: Type II Fiedler vector conserved across crystal open, crystal closed, and AF2-predicted structures (3/4, 75%). EGFR |FIS(AF)|=0.016/0.005; MMP9 0.045/0.068; CRBN 0.220/0.108. Conformational Lock Hypothesis: Type II network topology is sequence-determined, not crystal-packing-dependent. Type I/III proteins show |FIS(AF)|>0.80, confirming genuine multi-state topology. FIS pipeline open-source (fis_pipeline_n100.py), raw data included. Part of Geometric Systems Medicine series.