Skip to main content
. Author manuscript; available in PMC: 2016 Mar 1.
Published in final edited form as: Pharm Res. 2014 Sep 11;32(3):986–1001. doi: 10.1007/s11095-014-1511-3

Table II.

Comparison of various methods for predicting SoMs in the top-1, top-2, and top-3 positions.

X-ray structure aloneh
Randoma SMARTCyp Aloneb Vina Alonec Vina + SMARTCypd Vina + SMARTCyp+ QSARe
Top-1 12% 44% 21% 38% 49%
Top-2 24% 59% 27% 53% 56%
Top-3 38% 68% 37 % 60% 63%
% docked 64% Gamma 0.0g
Pseudo-apo Ensemblei
Vina Alonef Vina + SMARTCyp Vina+SMARTCyp + QSAR
Top-1 44% [28 ±6.5% ] 55% 88%
Top-2 58% [37 ±5.7% ] 77% 96%
Top-3 67% [48± 7.0% ] 88% 96%
% docked 96% [92±1.7% ] Gamma 23.5
a

Percentage of correctly predicted SoMs if a heavy atom was chosen at random for each ligand.

b

Percentage of correctly predicted SoMs using SMARTCyp only.

c

Percentage of correctly predicted SoMs using Autodock Vina alone. A prediction was considered “correct” if the true SoM was within 4.0Å in the top-1, top-2 or top-3 ranked docking poses, respectively.

d

Percentage of correctly predicted SoMs using a combination score comprised of the Vina score and the SmartCyp score, see Methods section for full details.

e

Percentage of correctly predicted SoMs using the modified QSAR model that includes the poses provided by Vina docking and the reactivity scores from SMARTCyp.

f

Bracketed values represent the percentage of successfully docked compounds when the protein structures that comprised the ensembles were chosen at random. These values represent the average and standard deviation over three randomly selected protein sets.

g

Although a gamma (γ) of 0 is selected, the omission of some atoms due to failure to find both a successful docking pose and SMARTCyp score can result in slightly different rankings using the CS versus SMARTCyp. These differences were caused by the inability to find a successful docking pose, therefore an atom may be ranked in SMARTCyp but not the combination approach, which can result in slight changes in the overall rankings as observed in the crystal structure.

h

Binding poses were identified using docking with AutoDock Vina to the x-ray structure of CYP2C9 only.

i

Binding poses were identified using docking with AutoDock Vina to an ensemble of proteins structures generated by an MD simulations based on the pseudo-apo form of CYP2C9 (holo x-ray structure with co-crystallized ligand removed).