Is the pyrimidine the proton-handling element of the genetic alphabet? A quantum-chemical test of a proton-centred account of infectious disease
Abstract
Abstract Background. Accounts of infectious disease are conventionally organised at the level of organism, gene and protein. A proton-centred alternative has been proposed, in which two elementary currencies — the electron, expressed through orbital hybridisation at biochemical nodes, and the proton, expressed through proton-motive force and nucleobase protonation — govern the establishment of infection, and in which the pyrimidines rather than the purines are the decisive participants. That proposal has until now been stated qualitatively. Here it is reduced to three falsifiable propositions and tested by density-functional calculation. Methods. Geometries, harmonic frequencies and thermochemistry were computed at M06-2X/def2-TZVP for 65 species, with aqueous energetics from C-PCM single points. The method was validated against 10 experimental gas-phase proton affinities (MAE 9.5 kJ/mol, r = 0.977) and against the experimental hydrogenation enthalpy and resonance energy of benzene. Results. Proposition 1 fails in the direction stated: at their most basic sites the pyrimidines average 885 kJ/mol against 945 kJ/mol for the purines, and the result holds on experimental values alone. The pyrimidines are instead the differentiated class, spanning 111 kJ/mol where the purines span 12; we reformulate the proposition accordingly and label the reformulation post hoc. Proposition 2 survives: the free-energy separation between dominant and mispairing tautomers moves from + 25.9 kJ/mol…
Read the paper
Related studies
- Chaos and quantum thermalization
- The Dalton quantum chemistry program system
- Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study
- Quantitative metabolomics by H-NMR and LC-MS/MS confirms altered metabolic pathways in diabetes
- Stable adiabatic quantum batteries
- A novel self-lipid antigen targets human T cells against CD1c(+) leukemias
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.