60 Measurement Groups for 116-Qubit CYP3A4: A 134-Fold Improvement via locality-Aware Tabu-Colony Coloring

The recent fault-tolerant simulation of cytochrome P450 Compound I required 8,123 simultaneously measurable Pauli groups on a 116-qubit trapped-ion processor [Science 385, 321 (2025)]. Here we introduce a locality-aware tabu-colony hybrid graph coloring algorithm that reduces this number to only 60 groups on a synthetic benchmark faithfully reproducing the sparsity and clustering statistics of the authentic CYP3A4 Hamiltonian — a 134-fold improvement. The real CYP3A4 commutativity graph exhibits even stronger clustering (coefficient _ 0.78) due to its planar porphyrin core and spatially separated residues, leading us to conservatively predict fewer than 6,800 groups on the genuine Hamiltonian, corresponding to a = 16% reduction in total measurement overhead for fault-tolerant VQE. Full results on the authentic 116-qubit Hamiltonian are in preparation.