. Author manuscript; available in PMC: 2024 Jul 11.

Published before final editing as: J Chem Theory Comput. 2023 Jan 11:10.1021/acs.jctc.2c00697. doi: 10.1021/acs.jctc.2c00697

Table 2:

The forward and reverse energy barriers for acetic acid and the absolute hydration free energy with different gti_add_sc flags.

Method	Phase	ΔG (syn/anti)	SC1	SC2	SC5
PMF profile (dummy state)	aq	ΔG^‡ (forward)	10.95	6.54	−0.10
		ΔG^‡ (reverse)	7.05	10.29	−0.03
		ΔG	3.90	−3.75	−0.07
	gas	ΔG^‡ (forward)	10.94	6.54	−0.10
		ΔG^‡ (reverse)	7.10	10.32	−0.01
		ΔG	3.84	−3.78	−0.09
Method	ΔG _hyd		SC1/R	SC2/R	ACES
TI with HREMD	starting in syn		4.57	4.41	6.06*
	starting in anti		9.60	9.64	5.95*
	differenc^†		5.03 ^†	5.23 ^†	0.11 ^†

All free energy values are in kcal/mol. The data for ΔG (syn/anti) is derived from the PMF profiles for acetic acid in the dummy state (λ=1) as defined by different gti_add_sc flags as follows.

gti_add_sc=1 (SC1): U^SC = U_bond + U_ang + U_LJ + U_tor + U_1–4LJ + U_dir + U_1–4Ele;

gti_add_sc=2 (SC2): U^SC = U_bond + U_ang + U_LJ + U_tor + U_1–4LJ.

gti_add_sc=5 (SC5): U^SC = U_bond + U_ang + U_LJ.

The data for the ΔG_hyd is the hydration free energy as defined by ΔG_hyd=ΔG_aq−ΔG_gas, where the ΔG_gas and ΔG_aq values are obtained from alchemical free energy simulations in the gas phase and in aqueous solution, respectively.

^†

The ideal result (in the sampling limit) result should be zero, i.e., ΔG_hyd should not depend on the starting conformation.