Pyrazolo[3,4-d]pyrimidines as inhibitor of anti-coagulation and inflammation

activity of Phospholipase A2: insight from molecular docking studies

Umesh Yadava*, Maheshwer Singh and Mihir Roychoudhury
Department of Physics, DDU Gorakhpur University, Gorakhpur -273009 INDIA

Figure S1
Hydrogen bonding and other non-covalent interactions in the best docking complexes as
obtained through GLIDE SP docking

Figure S2
Hydrogen bonding and other non-covalent interactions in the best docking complexes as
obtained through GLIDE XP docking

Molecules

Rank

Binding

Hydrogen Bonding

d(HA)

Angle

energy

(D_HA)

()

(D-HA)

1
2
3

1_1
1_1
1_1

(kcal/mol)
-5.63
-4.83
-6.87

N(LIG)-H O(ASP49)
N(LIG)-H O(ASP49)
N( LIG)-H O(GLY30)

1.729
1.818
1.999

()
146.91
164.30
137.30

4_1

-4.84

N( LIG)-H O(ASP49)
N( LYS69)-H..O(LIG)

2.129
2.002

133.76
151.80

1_1

-6.45

N(LYS69)-H...O (LIG)
N( LIG)-H O(GLY33)

2.123
1.861

156.69
142.07

6
7

1_1
1_1

-5.58
-6.91

N( LIG)-H O(ASP49)
N(HIS48)-H...O( LIG)

1.865
2.005

147.07
166.76

8
9
IMN

1_1
1_1
2_1

-6.23
-6.63
-6.29

N(LYS69)-H...O( LIG)
N( LIG)-H O(ASP49)
N(HIS48)-H O( LIG)
N(GLY30)-HO(LIG)
Table S1

1.899
1.747
2.013
2.047

156.49
135.58
141.70
163.73

Hydrogen bonding interactions in the best docking poses as obtained through AUTODOCK4.2

Table S2
Interactions in the docked complexes of Ligands with 3H1X as obtained through Glide Standard
Precision mode
Molecule

Entry

Docking

Glide

H-Bond

Distance

Angle

(SP)

ID

Energy

Score

stacking

(D-H...A)

(H...A)

(D-H-A)

32
76

(Kcal/mol)
-51.496
-45.644

-5.307
-4.791

interaction
His48
His48

(His48) N-H...N(Lig)
(His48) N-H...N(Lig)

()
2.144
2.211

()
143.7
144.5

-5.888

Tyr52
His48

(Lys69) N-H...N(Lig)
(His48) N-H...N(Lig)

2.024
2.305

144.0
138.1

(Lys69) N-H...N(Lig)

2.110

137.9

(Lig) C-H...O Gly30)

(His48) N-H...N(Lig)

2.312
2.403

112.6
128.9

(Lys69) N-H...N(Lig)

2.064

141.8

2.179
1.998
2.193
2.008

126.4
141.8
142.4
123.9

1
2
3

13

10

-53.361

-52.632

-6.213

His48

5
6
7

100
51
73

-49.149
-46.081
-43.893

-4.318
-5.208
-4.824

His48
His48
Tyr52

(Lig) C-H...O(Gly30)
(Lys69) N-H...O(Lig)
(His48) N-H...N(Lig)
(His48) N-H...O(Lig)

98

-40.195

-4.392

Lys69

(Lys69) N-H...O(Lig)
(His48) N-H...O(Lig)

2.422
2.359

138.6
139.0

Tyr52
..........

(Lys69) N-H...O(Lig)
(Lys69) N-H...O(Lig)
(Lys69) N-H...O(Lig)

2.010
1.757
1.682

123.5
156.0
172.8

9
IMN

95
121

-31.354
-29.019

-4.475
-3.243

Table S3
Interactions in the docked complexes of Ligands with 3H1X as obtained through Glide (Extra
Precision)

Molecule Entry

Docking

Glide

H-Bond

Distanc

Angle

ID

Energy

Score

stacking

(D-H...A)

e(H...A)

(D-H-A)

50

(Kcal/mol)
-51.919

-4.385

interaction
His48

(His48) N-H...N(Lig)

()
2.237

()
141.5

112

-46.207

-3.453

His48

(Lys69) N-H...O(Lig)
(His48) N-H...N(Lig)

2.165
2.286

132.8
146.9

(Lys69) N-H...N(Lig)
(His48) N-H...N(Lig)

2.046
2.275

135.6
136.3

(XP)

23

-53.376

-4.637

Tyr52
His48

22

-53.067

-4.689

His48

(Lys69) N-H...N(Lig)
(His48) N-H...N(Lig)

1.876
2.260

151.6
151.2

10

-49.792

-6.078

---------

(Lys69) N-H...N(Lig)
(Lys69) N-H...N(Lig)

2.031
2.003

150.4
142.3

1.826
2.106

153.9
143.6

117

-46.187

-3.382

His48

(His48) N-H...N(Lig)
(His48) N-H...N(Lig)

73

-42.095

-4.081

---------

(Lys69) N-H...N(Lig)
(His48) N-H...O(Lig)

2.144
2.096

134.5
137.6

Tyr52

(Lys69) N-H...O(Lig)
(His48) N-H...O(Lig)

2.880
2.277

136.5
135.7

--------..........

(Lys69) N-H...O(Lig)
(Trp31) N-H...O(Lig)
(Lys69) N-H...O(Lig)

2.013
1.966
1.762

129.6
144.5
152.1

(His48) N-H...O(Lig)

2.017

142.8

8
9
IMN

99
95
70

-50.349
-30.644
-24.344

-3.750
3.792
-4.109