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Docking Success Rate
The docking success rate was benchmarked as a percentage of correctly docked ligands for which the top-scored pose was within 2 Å RMSD from the reference ligand coordinates, for a set of protein-ligand complexes extracted from PDB. Although alternative definitions of docking success rate are available1 we used the most widely accepted one in order to make Lead Finder benchmarks comparable with competitive software benchmarks obtained elsewhere. Additionally, to increase reproducibility all docking calculations were performed independently 20 times, and docking was considered successful only when the probability of generating the top-ranked pose with 2 Å or better accuracy was at least 0.5.
A set of 407 protein-ligand complexes was used for current docking success rate measurements. This set of complexes was combined from test sets used in original benchmarking studies of such docking software as: FlexX2, Glide SP3, Glide XP4, Gold5,6,7, LigandFit8, MolDock9, Surflex10. For this reason, current benchmarking study of Lead Finder docking success rate appears to be the most extensive study of such kind; moreover, the results obtained with Lead Finder can be correctly compared to competitive docking programs of interest since they were obtained on the same sets of protein-ligand complexes. All benchmarking calculations were performed in two regimes (docking and screening, see Docking Algorithm section).
The docking success rate obtained with Lead Finder on different test sets ranged from 80.0% (for GlideXP and FlexX test sets) to 96.0% (for Surflex and MolDock test sets). The data in the table below show that Lead Finder outperformed all reviewed docking software programs for which reliable original benchmarks were available. More specifically, Lead Finder successfully docked 73 structures which could not be docked by FlexX, 52 structures - for Glide SP, 52 structures - for Glide XP, 30 structures - for Gold on the original Gold test set, 13 structures - for Gold on Astex diversity test set, 9 structures - for MolDock, 21 structures - for Surflex. Example of carboxypeptidase A inhibitor, which could not be correctly docked by such programs as Glide3 or FlexX2, but was successfully docked by Lead Finder, is illustrated in the figure.
CarboxypeptidaseA inhibitor successfully docked by Lead Finder. A — crystallographic pose (PDB structure 6cpa), B — ligand pose predicted by Lead Finder.

FlexX2

Glide SP3

Glide XP4

Gold5

Gold6

Gold7

LigandFit8

MolDock9

Surflex10

All

Original data

46.5

70.2

69.4

72.4

76.5

— a)

— b)

87.0

70.4

n/a

Lead Finder docking regime

85.0

82.3

81.3

87.3

90.6

92.4

87.3

96.1

96.3

85.0

Lead Finder screening regime

76.5

77.3

77.2

81.3

78.8

83.7

82.3

79.2

76.5

79.0

Number of structures

200

282

268

134

85

92

84

77

81

407

a) Data for the high-resolution subset (92 structures with resolution better than 2 Å) are not provided in original publication, only overall performance (over entire CCDC/Astex test of 224 structures) is given.
b) Original publication contains data only for 19 complexes, which is too small for comparative purposes. We extended this set by including additional 75 protein-ligand complexes which were used in original publication to benchmark LigandFit ability to detect active site cavity.
Docking success rate (%) of different software programs obtained on their native test sets and the current Lead Finder benchmarks in docking and screening regimes.
The docking success rate achieved by Lead Finder in the faster, less accurate screening regime was also higher than the original benchmarks obtained with competitive software, except MolDock. Such results were achieved by adjusting settings of the docking algorithm to minimize decrease in docking success rate while increasing the speed of calculations. The applicability of screening regime for high-performance calculations is illustrated in the Computing Speed section.

You can download complete description of current docking success rate benchmarking data including composition of the entire test set of 407 protein-ligand complexes by original test sets of FlexX, Glide SP, Glide XP, Gold, LigandFit, MolDock, Surflex docking programs.
 
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