Table 7 Summary of docking approach used, techniques for ligand and/or receptor flexibility,
and major features available in some chosen popular docking programs
Programs
Ligand flexibility
Receptor
flexibility
Major features in brief
AutoDock
[181]
Genetic algorithm
modeling
flexible residues
Force field-based scoring function,
uses averaged interaction energy grid
to account for receptor conformations
and simulated annealing for ligand
conformations
DOCK [159] Incremental build
Yes (through
AMBER score)
Force field- and contact score-based
scoring functions; docks either small
molecules or fragments, include
solvent effects
Glide [165]
Exhaustive search
No
Empirical score. Although, receptor
flexibility can be used in Induced fit,
Docking (IFD workflow) with Glide
and side chain rotations through
PRIME
GOLD [110] Genetic algorithm
Side chain
flexibility and
ensemble
docking
Empirical score, highly configurable
allowing to utilize chemical intuition
and domain expertise to improve pose
prediction and virtual screening
HADDOCK
[182]
Yes
Semi-flexible
torsion angle
refinement
Uses biochemical and/or biophysical
interaction data such as chemical shift
perturbation data resulting from NMR
titration experiments, mutagenesis
data, or bioinformatic predictions
LibDock
[183]
Rigid docking can use
programs in suit to
generate conformation
No
Docks a pre-generated set of
conformations for the ligand followed
by a final flexible gradient-based
optimization of the ligand in the
protein binding site
LigandFit
[184]
Monte Carlo
No
Empirical score, ligand conformation
docked into an active site based on
shape, followed by further CHARMm
minimization
Table 8 Summary of docking scoring/ranking results of chosen four inhibitors with known IC 50
values to PfPK5
Inhibitor
IC 50 (in nM)
RT ln(IC 50 )
(kcal/mol)
Docking score
LibDock
a
Gold
a
Dock6
b
Glide
b
OLM
15,000
−6.622
107.08(3)
55.56(4)
−56.46(3)
−5.75(3)
INR
5,500
−7.220
106.80(4)
64.56(2)
−55.04(4)
−8.65(1)
STA
1,000
−8.236
132.82(1)
60.98(3)
−64.55(2)
−4.99(4)
PVB
130
−9.453
130.25(2)
78.40(1)
−71.41(1)
−7.98(2)
Docking score from programs is given in cells of table, while rank is given in pair of parentheses.
Four docking programs, LibDock v2.3, Dock v6.7, Glide v7.0, and Gold v5.2, were used to dock
inhibitors in the PVB bound structure of PfPK5, after removing PVB. Inhibitors are tabulated from
top to bottom in increasing affinity order
a Higher positive score represents higher affinity
b
Higher negative score represents higher affinity
144
S. K. Panday and I. Ghosh
and major features available in some chosen popular docking programs
Programs
Ligand flexibility
Receptor
flexibility
Major features in brief
AutoDock
[181]
Genetic algorithm
modeling
flexible residues
Force field-based scoring function,
uses averaged interaction energy grid
to account for receptor conformations
and simulated annealing for ligand
conformations
DOCK [159] Incremental build
Yes (through
AMBER score)
Force field- and contact score-based
scoring functions; docks either small
molecules or fragments, include
solvent effects
Glide [165]
Exhaustive search
No
Empirical score. Although, receptor
flexibility can be used in Induced fit,
Docking (IFD workflow) with Glide
and side chain rotations through
PRIME
GOLD [110] Genetic algorithm
Side chain
flexibility and
ensemble
docking
Empirical score, highly configurable
allowing to utilize chemical intuition
and domain expertise to improve pose
prediction and virtual screening
HADDOCK
[182]
Yes
Semi-flexible
torsion angle
refinement
Uses biochemical and/or biophysical
interaction data such as chemical shift
perturbation data resulting from NMR
titration experiments, mutagenesis
data, or bioinformatic predictions
LibDock
[183]
Rigid docking can use
programs in suit to
generate conformation
No
Docks a pre-generated set of
conformations for the ligand followed
by a final flexible gradient-based
optimization of the ligand in the
protein binding site
LigandFit
[184]
Monte Carlo
No
Empirical score, ligand conformation
docked into an active site based on
shape, followed by further CHARMm
minimization
Table 8 Summary of docking scoring/ranking results of chosen four inhibitors with known IC 50
values to PfPK5
Inhibitor
IC 50 (in nM)
RT ln(IC 50 )
(kcal/mol)
Docking score
LibDock
a
Gold
a
Dock6
b
Glide
b
OLM
15,000
−6.622
107.08(3)
55.56(4)
−56.46(3)
−5.75(3)
INR
5,500
−7.220
106.80(4)
64.56(2)
−55.04(4)
−8.65(1)
STA
1,000
−8.236
132.82(1)
60.98(3)
−64.55(2)
−4.99(4)
PVB
130
−9.453
130.25(2)
78.40(1)
−71.41(1)
−7.98(2)
Docking score from programs is given in cells of table, while rank is given in pair of parentheses.
Four docking programs, LibDock v2.3, Dock v6.7, Glide v7.0, and Gold v5.2, were used to dock
inhibitors in the PVB bound structure of PfPK5, after removing PVB. Inhibitors are tabulated from
top to bottom in increasing affinity order
a Higher positive score represents higher affinity
b
Higher negative score represents higher affinity
144
S. K. Panday and I. Ghosh