Table 2.

Correlations of inhibitory potencies with the energy and SASA terms obtained by different methods for 28 MMP-9 inhibitors. The logK_i, K_i in M, values were used instead of ΔG_b in Eq. 1 and Eq. 3.

Method	Step	Eq.	a α×10−3 (mol/kcal)	b β×10−3 (mol/kcal)	c γ×10−3 (1/Å2)	κ	r2	SD	F	LOO d		LSO e
										q2	RMSE	q2	RMSE
FlexX f	1	-	69.7±63.71	-	-	−5.831±1.997	0.044	0.966	1.198	−0.079	0.989	−1.110	0.994
QM/MM Minimization	2	3	−0.420±1.190	-	12.30±3.12	−3.744±0.966	0.504	0.709	12.72	0.380	0.750	−0.457	0.808
QM/MM Minimization	2	3	-	-	11.55±2.26	−3.606±0.870	0.502	0.697	26.21	0.423	0.723	−0.278	0.751
MD	3	1	11.25±10.50	−4.090±6.010	8.380±1.240	−4.315±0.551	0.764	0.499	25.96	0.566	0.627	0.180	0.662
MD	3	1	4.630±4.060	-	8.680±1.150	−4.137±0.478	0.760	0.494	39.55	0.602	0.600	0.272	0.629
MD	3	1	-	-	9.230±1.105	4.399±0.422	0.747	0.496	76.91	0.717	0.506	0.442	0.531
QM/MM	4	3	3.592±0.580	-	7.543±0.727	−2.623±0.394	0.900	0.318	112.8	0.879	0.331	0.769	0.319

^aCharacterizes QM/MM interaction energy (Eq. 3) or van der Waals energy (Eq. 1).

^bCharacterizes electrostatic energy ( Eq. 1 only).

^cCharacterizes the solvent accessible surface area (Eq. 1 and Eq. 3).

^dLeave-one-out cross-validation.

^eLeave-several-out cross-validation: random selection of 6-member test set, repeated 200 times.

^fThe correlation between logK_i and the FlexX scores, with the slope α and the intercept κ.