Assessment of docking poses: interactions-based accuracy classification (IBAC) versus crystal structure deviations.
Six docking programs (FlexX, GOLD, ICM, LigandFit, the Northwestern University version of DOCK, and QXP) were evaluated in terms of their ability to reproduce experimentally observed binding modes (poses) of small-molecule ligands to macromolecular targets. The accuracy of a pose was assessed in two ways: First, the RMS deviation of the predicted pose from the crystal structure was calculated. Second, the predicted pose was compared to the experimentally observed one regarding the presence of key interactions with the protein. The latter assessment is referred to as interactions-based accuracy classification (IBAC). In a number of cases significant discrepancies were found between IBAC and RMSD-based classifications. Despite being more subjective, the IBAC proved to be a more meaningful measure of docking accuracy in all these cases.
Kroemer
Romano T
RT
Computational Sciences, Pharmacia Italia, Pfizer Group, Viale Pasteur 10, 20014 Nerviano, Milan, Italy. romano.kroemer@pharmacia.com
Vulpetti
Anna
A
McDonald
Joseph J
JJ
Rohrer
Douglas C
DC
Trosset
Jean-Yves
JY
Giordanetto
Fabrizio
F
Cotesta
Simona
S
McMartin
Colin
C
Kihlén
Mats
M
Stouten
Pieter F W
PF
D018360:Crystallography, X-Ray / Q000379:methods*; D008958:Models, Molecular; D015394:Molecular Structure