Genesis Human Proteome Scan: First Systematic Application of the Lo-Shu/Markov-Fiedler Geometric Framework to 20,158 Human Proteins — Druggability, Allosteric Prioritization, and Spectral Boundary Analysis

We apply the Lo-Shu/Markov-Fiedler geometric framework (validated at AUC=0.882, permutation p=0.005; DOI: 10.5281/zenodo.20153617) to a proteome-wide scan of the complete reviewed human proteome (UniProt, 20,431 proteins). Using AlphaFold v4 C-alpha structures, 20,158 proteins (98.66%) were processed in 72.3 minutes (0.21 s/protein, 8-thread parallel). Three prioritized candidate lists are reported: (1) Top druggable proteins (drug_score=1.0): includes E2F8, RBM47, ESYT2/3, SHTN1, ARHGAP10 — all with lambda_2 < 0.005 indicating well-connected multi-domain architecture. (2) Top allosteric candidates: MTRNR2L/Humanin-like peptide family (MTRNR2L3/5/6/9/10/13) dominate, with known neuroprotective and receptor-modulating functions (IGF-1R, FPRL1, CXCR4). (3) Top Markov-Fiedler spectral boundary proteins: Metallothionein family (MT1A/1G/1H/2A/1M) shows extreme spectral gap (> 0.30), consistent with their two-domain alpha/beta cluster architecture and known allosteric metal-sensing behavior. Cross-list analysis identifies MT1M (Q8N339) as a dual allosteric + spectral boundary candidate. All analyses use C-alpha only with no ligand information. Full 20,158-row dataset available upon request.