(a)
(b)
Fig. S1 Super-imposition of catalytic triad of 1VSH (ASV IN) and 1BL3 (HIV-1 IN) showing (a) two Zn2+ and one
Mg2+ (b) second Mg2+is inserted near to Glu152 by replicating second Zn 2+ coordinates. (generated by SPDB
viewer program and Pymol program)
Fig. S2 Docking interactions of molecule 29 into the active site of 1BL3. Blue color sticks represent active site
residues; Green color represents AutoDock conformation; Yellow color represents FlexX conformation; magenta
color represents Mg2+ (generated by PYMOL program)
Fig. S3 Docking interactions of molecule 34 into the active site of 1BL3. Blue color sticks represent active site
residues; Green color represents AutoDock conformation; Yellow color represents FlexX conformation; magenta
color represents Mg2+ (generated by PYMOL program)
Fig. S4 Docking interactions of molecule 35 into the active site of 1BL3. Blue color sticks represent active
site residues; Green color represents AutoDock conformation; Yellow color represents FlexX
conformation; magenta color represents Mg2+ (generated by PYMOL program)
Fig. S5 Docking interactions of molecule 39 into the active site of 1BL3. Blue color sticks represent active
site residues; Green color represents AutoDock conformation; Yellow color represents FlexX
conformation; magenta color represents Mg2+ (generated by PYMOL program)
Fig. S6 Docked pose of molecule 29 in to the active site of HIV-1 IN. Red sticks represent AutoDock
conformation; green color sticks represent FlexX conformation; magenta color balls represent Mg 2+
(generated by MOLCAD module of Sybyl7.1 package)
Fig. S7 Docked pose of molecule 32 in to the active site of HIV-1 IN. Red sticks represent AutoDock
conformation; green color sticks represent FlexX conformation; magenta color balls represent Mg 2+
(generated by MOLCAD module of Sybyl7.1 package)
Fig. S8 Docked pose of molecule 34 in to the active site of HIV-1 IN. Red sticks represent AutoDock
conformation; green color sticks represent FlexX conformation; magenta color balls represent Mg 2+
(generated by MOLCAD module of Sybyl7.1 package)
Fig. S9 Docked pose of molecule 35 in to the active site of HIV-1 IN. Red sticks represent AutoDock
conformation; green color sticks represent FlexX conformation; magenta color balls represent Mg 2+
(generated by MOLCAD module of Sybyl7.1 package)
Fig. S10 Docked pose of molecule 39 in to the active site of HIV-1 IN. Red sticks represent AutoDock
conformation; green color sticks represent FlexX conformation; magenta color balls represent Mg 2+
(generated by MOLCAD module of Sybyl7.1 package)
Fig. S11 Docking interaction of molecule 32 in to the active site of 1BL3. Blue color sticks represent
active site residues; red color sticks represent hydrophobic residues interacted with hydrophobic side
chain of ligand; Green color represents AutoDock conformation; Yellow color represents FlexX
conformation; Cyan color represents magnesium ion (generated by PYMOL program)
Comp
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Table S1 Actual and Predicted values of CoMFA model 1, 3, 4 and 5
Model-1 Model-3 Model-4 Model-5 Comp
Actual
Pred.
Pred.
Pred.
Pred.
Actual
pIC50
pIC50
pIC50
pIC50
pIC50
pIC50
4.00
3.99
4.11
4.14
4.22
21
6.40
4.00
3.67
3.67
3.89
4.04
22
6.30
4.00
4.28
4.24
4.28
4.27
23
6.15
4.00
3.92
3.79
4.01
4.07
24
5.85
5.05
4.35
4.56
4.38
4.56
25
5.22
4.00
3.94
4.12
4.12
4.36
26
6.15
4.00
4.28
4.34
4.34
4.42
27
5.80
4.00
3.88
3.9
4.07
4.22
28
6.52
4.00
4.10
3.9
3.96
3.84
29
6.70
4.00
4.02
3.84
4.01
3.78
30
5.52
6.30
6.26
5.96
6.08
5.81
31
6.00
4.00
4.08
4.27
4.14
4.01
32
6.70
4.00
3.98
4.25
4.19
3.93
33
5.92
6.30
6.31
6.36
6.08
5.98
34
6.70
4.00
4.14
4
4.41
4.12
35
6.70
4.00
4.02
3.85
4.46
4.17
36
5.55
5.77
5.93
5.77
5.79
5.82
37
6.15
4.00
3.95
4.09
3.84
3.97
38
5.59
4.00
4.06
4.02
3.86
3.98
39
6.70
6.52
6.20
6.4
5.94
6.25
Model-1
Pred.
pIC50
6.13
6.21
5.96
5.63
5.77
5.74
5.41
6.47
6.78
5.49
6.02
6.80
5.76
6.70
6.46
5.47
6.15
5.64
6.29
Model-3
Pred.
pIC50
6.77
6.3
5.85
5.61
5.83
5.86
5.62
6.54
6.78
5.92
5.99
6.59
6.35
6.72
6.36
5.46
6.31
5.68
6.52
Model-4
Pred.
pIC50
6.06
6.36
5.83
5.84
5.92
6.23
5.96
6.5
6.71
5.95
6.13
6.64
6.12
6.61
6.49
5.38
6.23
5.63
6.91
Model-5
Pred.
pIC50
6.41
6.61
6.43
5.30
5.88
5.74
5.48
6.39
6.67
5.95
6.06
6.57
6.29
6.72
6.83
5.48
6.29
5.83
6.54
Fig. S12 Scatter plot of CoMFA model 2 for Actual versus Predicted pIC50 for (a) training set and (b) test
set
(a)
(b)
Fig. S13 CoMFA (model-1) (a) steric and (b) electrostatics contour maps: green contour represent
sterically favored regions; yellow contour represent sterically disfavored regions; red contour represent
negative potential favored; blue contour represent positive potential favored. The sticks represent
molecule 29 in to the active site of HIV-1 IN
(a)
(b)
Fig. S14 CoMFA (model-3) (a) steric and (b) electrostatics contour maps: green contour represent
sterically favored regions; yellow contour represent sterically disfavored regions; red contour represent
negative potential favored; blue contour represent positive potential favored. The sticks represent
molecule 34 in to the active site of HIV-1 IN
(a)
(b)
Fig. S15 CoMFA (model-4) (a) steric and (b) electrostatics contour maps: green contour represent
sterically favored regions; yellow contour represent sterically disfavored regions; red contour represent
negative potential favored; blue contour represent positive potential favored. The sticks represent
molecule 35 in to the active site of HIV-1 IN
(a)
(b)
Fig. S16 CoMFA (model-5) (a) steric and (b) electrostatics contour maps: green contour represent
sterically favored regions; yellow contour represent sterically disfavored regions; red contour represent
negative potential favored; blue contour represent positive potential favored. The sticks represent
molecule 39 in to the active site of HIV-1 IN
Table S2 Common Pharamcophore Mapping results of training set
Hypothesis No.
Features
Rank
DH
PH
MaxFit
Hypo1
RDAA
134.106
1111
0000
4
Hypo 2
RAAA
134.106
1111
0000
4
Hypo 3
RDAA
133.961
1111
0000
4
Hypo 4
RDAA
133.580
1111
0000
4
Hypo 5
RDAA
133.467
1111
0000
4
Hypo 6
RAAA
133.467
1111
0000
4
Hypo 7
RDAA
132.828
1111
0000
4
Hypo 8
RAAA
132.828
1111
0000
4
Hypo 9
RAAA
132.656
1111
0000
4
Hypo 10
RDAA
132.451
1111
0000
4
D-Hydrogen bond donor, A- Hydrogen bond acceptor, R-Ring aromatic, DH-Direct hits, PH- Partial hits
The direct hit (DH) 1 indicates training set molecule mapped every feature in the hypothesis. The
numbers correspond to the molecules (from top to bottom) in the spreadsheet. For this hypothesis, all five
molecules mapped all hypothesis features. The partial hit (PH) 0 indicates molecule mapped all but one
feature in the hypothesis. These hit masks give us a quick way to compare common-features hypotheses.
Table S3 Best model (Hypo-1) results for training set (highly active) molecules used for model generation
Name
Activity
Fit Value
RDAA
Principal
MaxOmitFeat
2
0
curcumine-33
4.00
1111
5.92
2
0
curcumine-38
3.25
1111
5.59
2
0
curcumine-36
3.16
1111
5.55
2
0
curcumine-35
2.80
1111
6.70
2
0
curcumine-20
2.50
1111
6.52
2
0
curcumine-23
2.48
1111
6.15
2
0
curcumine-11
2.41
1111
6.30
2
0
curcumine-32
2.23
1111
6.70
2
0
curcumine-21
2.10
1111
6.40
2
curcumine-27
1.92
1111
5.80
2
curcumine-24
1.53
1111
5.85
2
curcumine-28
0.92
1111
6.52
R- Ring aromatic, D-Hydrogen bond donor, A- Hydrogen bond acceptor, 1 means fit
corresponding feature.
0
0
0
well with
Table S4 Test set molecules results after screening from best model
Name
Activity
Fit value
RDAA
curcumine-37
4.00
1111
6.15
curcumine-34
3.93
1111
6.70
curcumine-39
3.93
1111
6.70
curcumine-17
3.31
1111
5.77
curcumine-26
3.24
1111
6.15
curcumine-22
3.21
1111
6.30
curcumine-14
2.77
1111
6.30
curcumine-29
2.33
1111
6.70
Fig. S17 Best ranked pharmacophore model (Hypo-1) aligned with molecule 37 (test set) generated by
common pharmacophore mapping method (Accelrys Discovery Studio 5.2). Green color spheres
represent hydrogen bond acceptor; Magenta color sphere represent hydrogen bond donor; Yellow color
represents ring aromatic feature
Fig. S18 Best ranked pharmacophore model (Hypo-1) aligned with molecule 34 (test set) generated by
common pharmacophore mapping method (Accelrys Discovery Studio 5.2). Green color spheres
represent hydrogen bond acceptor; Magenta color sphere represent hydrogen bond donor; Yellow color
represents ring aromatic feature
Table S5 CoMFA predicted values of MBS derivatives obtained from 3D database screening using
common pharmacophore model of highly active molecule
Molecule
Fit Score Actual pIC50 Pred. pIC50
Molecule
Fit Score Actual pIC50 Pred. pIC50
MBS-48
3.84
MBS-5
2.68
5.30
4.09
4.81
4.24
MBS-35
3.81
MBS-37
2.66
3.85
4.39
3.68
4.81
MBS-74
3.65
MBS-3
2.65
5.05
4.53
4.81
4.65
MBS-53
3.55
MBS-23
2.65
4.18
3.61
5.03
4.53
MBS-78
3.38
MBS-2
2.65
4.36
4.10
4.65
4.62
MBS-44
3.35
MBS-7
2.65
5.12
4.35
4.63
4.69
MBS-77
3.32
MBS-4
2.64
3.38
4.40
5.20
4.68
MBS-31
2.96
MBS-25
2.62
3.92
4.38
4.76
4.78
MBS-43
2.92
MBS-8
2.57
4.31
3.80
4.79
4.67
MBS-42
2.82
MBS-19
2.30
3.87
4.28
5.44
4.89
MBS-1
2.81
MBS-22
2.26
4.79
4.62
4.84
4.86
MBS-54
2.79
MBS-20
1.95
4.64
4.03
5.03
5.00
MBS-6
2.69
MBS-52
1.84
4.56
4.71
4.22
3.78
MBS-41
2.69
MBS-51
0.98
3.89
3.89
4.71
3.90
MBS-62
2.69
MBS-55
0.83
4.82
4.85
4.22
4.89
O
S N
O
O
HN
H
N
N
N
OH
OH
35
48
O
Cl
N N
HN
O
O
S
O
N N
N
H
N
Cl
HO
O
S
N
H
78
HN
O
53
O
O
HO
HS
Cl
N NH
O
N
N
H
S
S
O
N
N
N
H 2N
NH 2
H 2N
N
N
N
O
HN
S O
O
O
N
HN
Cl
N
43
HN
S
O
O
N
NH
O S
O
O
N N
O
44
N
N
O
O
O
HN
N
NH
S
S
O
NH
74
S
N
N
O
HS
N
N
N
HN
O
S
N
N
N
HO
HN
NH
S
O
O
N
S
N N
O
77
NH
S
O
O
N
N
N
O
42
Cl
31
H
N N
SH
HN
S
O
O
N
1
N
H
N
N
S
NH
S
O
O
N
N
HN
Cl
OH
O
S
N
SH O H
54
O
N
NO 2
HS
N
NH
O S
62
O
H
N
O
HS
N
H
N N
O
Cl
O
Cl
5
O
N
H
N
N
N
N
H
Cl
HN
Cl
O
Cl
S
S
O
O
N
F Cl
F
HN
O
N
S
N
HS
O
23
O
S
Cl
O
4
O
N
H
N
N
2
N
H
SH
O
S NH
N
O
N
25
N
H2 N
SH
Cl
O N
N
S
N
N
SH O H
22
S
N
N
NH2
Cl
N
N
O
HN S
N
N
O
N
OH O
52
N
OH
N
OH
51
O
NH
N
O
S NH 2
O
N
N
S
37
OH
H
N
O
N
N
H
N
N
O
F
N
N
N
41
Cl
N
N
O
N
S N
O H
SH
19
Cl
O N
N
S
N
N
SH O H
8
O O
N N
S
N
S
N
H
SH
N
20
6
NH 2
N
S
N
SH O H
7
N
Cl
S
N
SH O H
N
O
NH
S
O
N
NH
S
O
O
O
HN
N
S
N
HS
N
N
H
NH
S
O
O
N N
H
3
Cl
Cl
OH
O
55
Fig. S19 Structures of MBS molecules shown in Table-S5
N
HN
S
N
O O
Fig. S20 Best ranked pharmacophore model (Hypo-1) aligned with MBS-48 (screened molecule)
generated by common pharmacophore mapping method (Accelrys Discovery Studio 5.2). Green color
spheres represent hydrogen bond acceptor; Magenta color sphere represent hydrogen bond donor;
Yellow color represents ring aromatic feature