Table 1.

Calculated relative binding free energies (kJ/mol), obtained with three different sets of charges for the ligands (RH, BA and BH) and two perturbed groups (SP or LP)

	RH/SP	RH/LP	BA/SP	BA/LP	BH/SP	BH/LP	Consensus	Exp.
OMe → OH	0.2 ± 0.4	1.0 ± 0.7	− 0.8 ± 0.4	1.6 ± 0.6	− 0.6 ± 0.4	0.9 ± 0.6	0.4 ± 0.4	0.6 ± 0.3
NHMe → OMe	− 0.8 ± 0.3	− 3.3 ± 0.6	− 6.0 ± 0.4	− 4.8 ± 0.6	− 6.7 ± 0.4	− 6.4 ± 0.6	− 4.7 ± 0.9	0.0 ± 0.3
NMe2 → NHMe	− 5.8 ± 0.5	− 4.4 ± 0.7	− 1.6 ± 0.5	− 1.1 ± 0.6	− 3.2 ± 0.5	− 2.2 ± 0.7	− 3.0 ± 0.7	− 2.0 ± 0.2
NMe2 → NH2	− 1.7 ± 0.5	− 2.9 ± 0.7	− 3.9 ± 0.5	− 3.6 ± 0.7	− 2.9 ± 0.5	− 5.1 ± 0.7	− 3.3 ± 0.5	− 3.2 ± 0.2
OEt → OMe	− 2.8 ± 0.4	2.7 ± 0.7	− 4.2 ± 0.4	− 1.4 ± 0.6	− 3.3 ± 0.4	− 2.7 ± 0.6	− 1.9 ± 1.0	− 4.0 ± 0.4
Pyr → F	− 10.4 ± 0.6	− 7.5 ± 0.8	− 10.4 ± 0.6	− 9.1 ± 0.7	− 9.0 ± 0.6	− 8.3 ± 0.7	− 9.1 ± 0.5	− 11.2
OH → F	− 0.4 ± 0.2	− 2.1 ± 0.6	1.7 ± 0.2	− 1.0 ± 0.5	1.0 ± 0.2	− 0.4 ± 0.6	− 0.2 ± 0.6	− 4.8 ± 0.2
MAD	1.8 ± 0.2	2.8 ± 0.3	2.3 ± 0.2	2.2 ± 0.3	2.6 ± 0.2	2.5 ± 0.3	2.1 ± 0.3
RMSD	2.3 ± 0.2	3.4 ± 0.3	3.4 ± 0.2	2.7 ± 0.3	3.5 ± 0.2	3.3 ± 0.3	2.7 ± 0.3
MSD	0.4 ± 0.2	1.1 ± 0.3	− 0.1 ± 0.3	0.7 ± 0.3	0.0 ± 0.3	0.0 ± 0.3	0.4 ± 0.3
Max	4.3 ± 0.3	6.6 ± 0.8	6.4 ± 0.3	4.8 ± 0.6	6.7 ± 0.4	6.4 ± 0.7	4.7 ± 0.7
R 2	0.79 ± 0.03	0.54 ± 0.07	0.61 ± 0.04	0.71 ± 0.06	0.55 ± 0.04	0.60 ± 0.06	0.71 ± 0.06
τr	1.00 ± 0.16	0.67 ± 0.10	0.33 ± 0.08	1.00 ± 0.13	0.33 ± 0.10	1.00 ± 0.18	1.00 ± 0.22
τr90	1.00 ± 0.04	0.60 ± 0.02	0.33 ± 0.08	1.00 ± 0.13	0.60 ± 0.04	1.00 ± 0.00	1.00 ± 0.08

Experimental relative affinities are given in the last column [38]