. 2023 Mar 22;158(12):124110. doi: 10.1063/5.0139281

TABLE IV.

Selected relative protonation/deprotonation energies from ωB97X/6-31G* and model error (kcal/mol) relevant to acid/base catalysis in RNA cleavage reactions.^a

		QM/Δ-MLP or MLP			DFTB			NDDO
	ωB97X	QDπ	AIQM1	ANI-2x	GFN2	DFTB3	ChIMES	ODM2	D3H4X	PM7
Protonation pair	ΔE	Err	Err	Err	Err	Err	Err	Err	Err	Err
[Lys:NH₂,iPrOH]	167.76	0.00	‒0.64	‒115.04	0.04	6.11	‒6.87	‒15.24	‒13.15	‒10.15
[His:N_ϵ,iPrOH]	158.33	0.08	‒9.22	‒126.62	‒7.02	‒11.33	‒17.47	‒18.74	‒12.96	−6.19
[EtO⁻,His:N_ϵH⁺]	‒160.25	‒0.02	12.82	137.70	9.66	11.71	18.09	21.92	12.24	5.36
[ ${G:N}_{1}^{-}$ ,iPrOH]	43.06	‒1.11	‒1.15	‒28.62	−2.69	‒8.63	‒11.17	‒10.84	0.89	5.45
[EtO⁻,A:N₁H⁺]	‒165.06	1.25	12.94	137.24	10.02	15.21	23.15	20.74	8.07	1.25
[EtO⁻,A:N₃H⁺]	‒190.89	1.21	12.88	143.42	11.40	16.00	24.17	19.43	17.97	8.39
[EtO⁻,C:N₃H⁺]	‒160.33	0.89	12.78	145.20	6.58	4.66	16.93	20.19	7.03	2.22
[ ${G:N}_{1}^{-}$ ,A:N₁H⁺]	‒120.07	0.08	8.19	97.55	4.69	6.20	11.36	6.73	9.69	7.53
[ ${G:N}_{1}^{-}$ ,A:N₃H⁺]	‒145.91	0.04	8.12	103.73	6.07	6.99	12.38	5.41	19.58	14.67
[ ${G:N}_{1}^{-}$ ,C:N₃H⁺]	‒115.34	‒0.27	8.03	105.50	1.25	‒4.35	5.14	6.17	8.64	8.51
maE	…	0.50	8.68	114.06	5.94	9.12	14.67	14.54	11.02	6.97
rmsE	…	0.72	9.72	118.72	6.96	9.96	15.87	15.84	12.17	7.88

^{^a}

Models and datasets are described in Sec. II. Protonation pairs are written in the general form as follows: [B, A]: B + A → BH⁺ + A⁻, or [B⁻, AH⁺]: B⁻ + AH⁺ → BH + A. Here, B/BH⁺ and B⁻/BH are the base/conjugate acid pairs and A/A⁻ and AH⁺/A are the acid/conjugate base pairs. These are model systems for general acid and base catalysis in RNA cleavage reactions by small nucleolytic ribozymes and ribonucleases.¹⁰⁰ The molecules indicated are isopropanol (iPrOH), ethoxide (EtO⁻), neutral lysine (Lys:NH₂), neutral histidine (His:N_ϵ), protonated histidine (His:N_ϵH⁺), deprotonated guanine at the N1 position ( ${G:N}_{1}^{-}$ ), protonated adenine at the N1 and N3 positions (A:N₁H⁺ and A:N₃H⁺), and protonated cytosine at the N3 position (C:N₃H⁺).