Table 1.

Calculated PDLD/S-LRA/β, LRA/β and LIE absolute binding free energies and the corresponding observed values.^a

Enzyme/class	PDLD/S-LRA/β			LRA/β		LIE
	$\mathrm{\Delta }{G}_{\mathit{bind}}^{\mathit{calc}}$εp = 4 (εp = 20) β=0.25 (default)	$\mathrm{\Delta }{G}_{\mathit{bind}}^{\mathit{calc}}$εp = 4 (εp = 20) (fitting)	Fast version ε p = 4 (ε p = 20) β=0.25 (default)	$\mathrm{\Delta }{G}_{\mathit{bind}}^{\mathit{calc}}$εp = 1 β=0.25 (default)	$\mathrm{\Delta }{G}_{\mathit{bind}}^{\mathit{calc}}$εp = 1 (fitting)	$\mathrm{\Delta }{G}_{\mathit{bind}}^{\mathit{calc}}$εp = 1 β=0.25 (default)	$\mathrm{\Delta }{G}_{\mathit{bind}}^{\mathit{calc}}$εp = 1 (fitting)	$\mathrm{\Delta }{G}_{\mathit{bind}}^{\mathit{calc}}$
Chorismate mutase (Isomerase)103		β=0.30			β=0.50		β=0.51
1*	−15.50 (−8.68)	−15.99 (−9.17)	−15.53 (−8.59)	−8.15	−8.39	−6.16	−7.32	−8.30
2*	−15.44 (−8.80)	−15.87 (−9.23)	−19.65 (−12.76)	−8.74	−9.00	−8.47	−9.07	−9.00
3*	−4.94 (−4.66)	−5.11 (−4.83)	−5.20 (−4.52)	−5.22	−3.92	−5.11	−4.74	−5.00
Thrombin (Hydrolase)82		β=0.30			β=0.35		β=0.41
4*	−8.67 (−9.99)	−10.26 (−11.59)	−8.99 (−10.21)	−12.85	−11.55	−10.06	−11.55	−11.42
5*	−9.46 (−10.06)	−11.29 (−11.89)	−9.20 (−9.72)	−9.09	−9.99	−6.58	−9.47	−11.41
Trypsin (Hydrolase)82		β=0.26			β=0.35		β=0.45
6*	−8.35 (−7.77)	−8.56 (−7.98)	−9.01 (−8.62)	−9.37	−8.24	−7.27	−8.62	−8.69
7*	−10.39 (−9.94)	−10.56 (−10.11)	−10.42 (−9.32)	−10.72	−9.37	−9.59	−9.15	−9.75
8*	−10.68 (−10.49)	−10.93 (−10.74)	−10.84 (−9.98)	−10.97	−9.56	−11.55	−11.57	−10.20
Renin (Aspartyl protease)104		β=0.22			β=0.40		β=0.53
9	−9.55	−9.12	−9.19	−10.16	−9.44	−9.76	−9.75	−9.78
10	−10.28	−9.72	−9.98	−9.56	−9.07	−9.50	−9.41	−9.77
11	−8.64	−8.15	−8.50	−8.15	−7.71	−7.23	−8.72	−7.50
HIV Protease (Aspartyl protease)105		β=0.25			β=0.51		β=0.64
12	−10.34	−10.34	−8.69	−10.88	−10.40	−6.89	−10.39	−10.40
Aldose Reductase (Oxidoreductase)106		β=0.30			β=0.25		β=0.25
13*	−8.69 (−7.12)	−9.91 (−8.34)	−6.70 (−5.50)	−8.30	−8.30	−8.32	−8.32	−8.46
Trypsin (Hydrolase)107		β=0.30			β=0.60		β=0.80
14*	−3.24 (−4.16 )	−3.76 (−4.68)	−3.37 (−4.43)	−6.46	−6.23	−4.34	−6.00	−6.35
T4 lysozyme (Hydrolase) 83,93,108		β=0.33			β=0.80		β=0.80
15	−4.34	−5.08	−2.92	−3.23	−4.50	−3.16	−4.40	−5.19

^aAll binding free energies are in kcal/mol.

All charged ligands have been denoted by ‘*’. Note that ‘α’ denotes the electrostatic term in our study while it represents the non-electrostatic β term in studies by Åqvist and coworkers¹³,⁴² In the PDLD/S-LRA/β studies, the first column corresponds to the calculations where the protein groups are ionized with ε_p = 4, and ε_p = 20, the second column provides fitted values for column 1 and the third column corresponds to the fast version described in the main text. (For details, see Table S1 and S2; supporting information).