Searching for bioactive conformations of drug-like ligands with current force fields: how good are we?

Table 2 Fraction (%) of ligands similar to the reference crystal pose depending on charge and solvent

Force field	Charged (I)		Neutralized (II)		Combined (III)
Force field	<0.5 Å	<1.0 Å	<0.5 Å	<1.0 Å	<0.5 Å	<1.0 Å
OPLS2005-chloroform	38.6	68.4	43.5	77.1	47.3	79.9
OPLS2005-octanol	40.8	71.1	45.0	77.5	48.9	80.1
OPLS2005-water	39.9	76.9	47.1	82.2	49.6	84.7
MMFFs-chloroform	35.8	67.6	43.4	74.4	46.1	77.9
MMFFs-octanol	40.4	71.1	45.1	79.1	48.2	82.3
MMFFs-water	40.9	77.4	47.3	81.7	50.2	84.3
AMBER-chloroform	36.7	67.5	43.0	75.0	46.2	77.8
AMBER-octanol	38.3	69.2	44.7	76.0	46.6	78.2
AMBER-water	43.1	77.4	45.5	79.0	48.6	81.3
OPLS3-chloroform	39.6	69.3	46.8	74.2	49.9	79.0
OPLS3-octanol	43.8	74.4	50.2	79.0	53.4	82.1
OPLS3-water	47.8	81.6	53.5	81.7	57.4	86.8

Conformer RMSDs were calculated taking crystal pose as reference for; (I) conformational search performed with charged input structures, (II) conformational search performed with neutralized input structures, (III) combined pool of (I) and (II)

ISSN: 1758-2946