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Table 5 Analysis of the reasons for the 9 targets ranking failure

From: Efficient conformational sampling and weak scoring in docking programs? Strategy of the wisdom of crowds

Target

RMSD (Ã…) of the best best-pose

RMSD (Ã…) of the best top-rank pose

Reasons for incorrect ranking

Due to the scoring functions?

Possible recommendations

cp3a4

2.03

Surflex

4.14

Glidescore

Coordination bond

No

 

xiap

1.25

Surflex

3.78

FlexX

Ligand not well anchored in the binding site

No

 

hdac8

0.91

Glidescore

2.91

Goldscore

The metal ion chelation is not considered explicitly or not well parametrized

Yes

With modified parameters of the metal, the top-rank pose is correct

hs90a

0.32

Gold

9.54

Glidescore, FlexX, Goldscore

An off-center pose is privileged

No

Possibility of the existence of a secondary site difficult to reach (dynamical considerations)

igf1r

0.72

Surflex

2.32

Surflex

Difference in protonation

No

Include in situ protonation in the docking procedure

cxcr4

1.94

Gold

2.95

Surflex

Difference in protonation

No

Similar to igf1r

pnph

0.65

Gold

3.14

Glidescore

Difference in protonation

No

Similar to igf1r

hivpr

1.97

Surflex

2.26

Glidescore, Goldscore

The difference is located in a loose or exposed to solvent part of the ligand

No

The difference is not a problem

tysy

1.27

Surflex

2.7

Goldscore

The difference is located in a loose or exposed to solvent part of the ligand

No

Similar to hivpr

  1. For each ligand, all poses of the pool were ranked by each program and we only consider the top-rank pose with the smallest RMSD, without any consideration of the program