Table I. Free energy in reduced model of... | Rockefeller University Press

Table I.

Free energy in reduced model of the binding site S2 in KcsA (kcal/mol)

Systems	$Δ G_{Na . K}^{bulk}$	$Δ G_{Na . K}^{site}$	$Δ Δ G_{Na,K}$
Non-polarizable force field; Yu et al., 2010b ^a	−18.3	−12.1	6.2
Polarizable force field^a	−17.3	−8.8	8.5
DFT^b	−25.6	−21.5	4.1

Systems	$Δ G_{Na . K}^{bulk}$	$Δ G_{Na . K}^{site}$	$Δ Δ G_{Na,K}$
Non-polarizable force field; Yu et al., 2010b ^a	−18.3	−12.1	6.2
Polarizable force field^a	−17.3	−8.8	8.5
DFT^b	−25.6	−21.5	4.1

Details about the features of the reduced model and the computations for the non-polarizable force field are given in Yu et al. (2010b). The model system is comprised of one ion (K⁺ or Na⁺) surrounded by four diglycine residues representing the carbonyl groups of Val76 and Gly77. The protein atoms are confined to small spherical volumes deduced from an analysis of all-atom MD trajectories of the full-length KcsA in a lipid bilayer. The FEP/MD simulations were carried out via the PERT module of the program CHARMM (Brooks et al., 2009) using Langevin dynamics. The computations with the Drude polarizable force field were carried out using the same procedure with the ion parameters of Yu et al. (2010c).

DFT FEP calculations were performed at the PBE/DZVP level of theory (Perdew et al., 1996) using the CHARMM/DeMon2k interface (Lev et al., 2010; Zhang et al., 2010). The DFT relative free energy difference for the ions in bulk was calculated using 16 water molecules restrained within a spherical volume around the ion, mimicking the bulk density. The FEP/MD simulations were carried out using 11 evenly spaced windows for a thermodynamic coupling parameter varying from 0 to 1, with 10 ps of sampling per window.

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