English

Auditing Haldane Consistency in Reversible Enzyme Kinetics: A Curated Two-Sided Backbone and a Labeled Fold-Error Benchmark

Chemical Physics 2026-07-02 v1 Biological Physics

Abstract

Reversible enzyme kinetic constants can be audited through the Haldane relation: the apparent equilibrium constant implied by the rate law should match biochemical thermodynamics under matched conditions. We use the reciprocal cost CHaldane=J(Keq,kin/Keq,thermo)C_{\mathrm{Haldane}}=J(K'_{\mathrm{eq,kin}}/K'_{\mathrm{eq,thermo}}), with J(x)=12(x+x1)1=cosh(lnx)1J(x)=\tfrac12(x+x^{-1})-1=\cosh(\ln x)-1, as a calibrated, direction-symmetric reporting scale. The score is zero at agreement, penalizes reciprocal over- and underestimates equally, encodes the free-energy discrepancy in RTRT units, and ranks records identically to ΔΔG|\Delta\Delta G|; the contribution is therefore biochemical curation, a reproducible workflow, and fold-error calibration rather than a new ordering. We apply the score to a curated demonstration set and, under prespecified inclusion criteria, assemble a two-sided backbone of twenty-one audited single-study records. Eight genuinely independent tests pair kinetics fit without a thermodynamic prior against separately measured equilibria; all eight fall within twofold (maximum CHaldane=0.069C_{\mathrm{Haldane}}=0.069), although this remains a feasibility demonstration. Across the full backbone, eighteen records fall within twofold and three are flagged. The backbone is concentrated in carbohydrate isomerases and epimerases, so these results are within-family observations. Because real records carry no ground-truth labels, a semi-synthetic benchmark (twenty-nine within-twofold seeds, 1,8851{,}885 injected known-error cases) quantifies detectability: AUC 0.7840.784 (95%95\% bootstrap CI 0.7250.725--0.8380.838), conditional on the injected error taxonomy and invariant under monotone rescaling of lnx|\ln x|. All data, code, protocol, and benchmark generator are archived for exact reproduction.

Keywords

Cite

@article{arxiv.2607.02784,
  title  = {Auditing Haldane Consistency in Reversible Enzyme Kinetics: A Curated Two-Sided Backbone and a Labeled Fold-Error Benchmark},
  author = {Megan Simons and Jonathan Washburn},
  journal= {arXiv preprint arXiv:2607.02784},
  year   = {2026}
}

Comments

50 pages, 8 figures, supplementary material and reproducibility code/data included as ancillary files