[2603.25880] Spectral Coherence Index: A Model-Free Metric for Protein Structural Ensemble Quality Assessment

Quantitative Biology > Quantitative Methods arXiv:2603.25880 (q-bio) [Submitted on 26 Mar 2026] Title:Spectral Coherence Index: A Model-Free Metric for Protein Structural Ensemble Quality Assessment Authors:Yuda Bi, Huaiwen Zhang, Jingnan Sun, Vince D Calhoun View a PDF of the paper titled Spectral Coherence Index: A Model-Free Metric for Protein Structural Ensemble Quality Assessment, by Yuda Bi and 3 other authors View PDF HTML (experimental) Abstract:Protein structural ensembles from NMR spectroscopy capture biologically important conformational heterogeneity, but it remains difficult to determine whether observed variation reflects coordinated motion or noise-like artifacts. We evaluate the Spectral Coherence Index (SCI), a model-free, rotation-invariant summary derived from the participation-ratio effective rank of the inter-model pairwise distance-variance matrix. Under grouped primary analysis of a Main110 cohort of 110 NMR ensembles (30--403 residues; 10--30 models per entry), SCI separated experimental ensembles from matched synthetic incoherent controls with AUC-ROC $= 0.973$ and Cliff's $\delta = -0.945$. Relative to an internal 27-protein pilot, discrimination softened modestly, showing that pilot-era thresholds do not transfer perfectly to a larger, more heterogeneous cohort: the primary operating point $\tau = 0.811$ yielded 95.5\% sensitivity and 89.1\% specificity. PDB-level sensitivity remained nearly unchanged (AUC $= 0.972$), and an independent 11-protei...