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Table 1 Substrate phosphorylation by ATP, kcat/Km, IC50 and predicted interaction energy for protein–ligand pairs

From: A computational protocol to evaluate the effects of protein mutants in the kinase gatekeeper position on the binding of ATP substrate analogues

Kinases

Ligands

Experimental data

Predicted interaction energies (kcal/mol)

JNK kinase

 

% Substrate phosphorylation

 

JNK

N6-(benzyl)

99

0a

 

N6-(2-phenythyl)

98

0a

 

N6-(cyclopentyl)

97

0a

 

N6-(1-methylbutyl)

93

0a

JNKM108GL168A

N6-(benzyl)

62

−17.34

 

N6-(cyclopentyl)

59

−14.42

 

N6-(1-methylbutyl)

47

−20.42

 

N6-(2-phenythyl)

8

−33.0

v-Src tyrosine kinase

 

kcat/Km (min −1 M −1 )

 

v-Src

ATP

1.6*105

−21.35

v-SrcI338A

 

1.4*104

−19.91

v-SrcI338G

 

1*104

−19.01

v-Src

N6-(benzyl) ATP

0

0a

v-SrcI338A

 

2.5*104

−14.92

v-SrcI338G

 

4.0*104

−29.17

Tyrosine and serine/threonine kinases

 

IC 50 (μM)

 

v-Src

PP1

5 ± 2

0a

v-SrcI338F

 

8 ± 2

0a

v-SrcI338 M

 

8 ± 1

0a

v-SrcI338S

 

0.4 ± 0.05

−28.78

v-SrcI338T

 

0.1 ± 0.02

−33.32

v-SrcI338 V

 

0.1 ± 0.02

−27.41

v-SrcI338C

 

0.07 ± 0.02

−27.44

v-SrcI338A

 

0.005 ± 0.002

−39.26

v-SrcI338G

 

0.005 ± 0.002

−38.56

Fyn

 

0.05 ± 0.02

−36.81

FynT339A

 

0.005 ± 0.002

−36.21

Abl

 

0.3 ± 0.03

−32.93

AblT334A

 

0.03 ± 0.005

−33.86

CamKII

 

80 ± 10

0a

CamKIIF89G

 

0.5 ± 0.1

−15.74

Cdk2

 

50 ± 10

0a

Cdk2F80G

 

0.16 ± 0.03

−24.85

P38

 

0.82 ± 0.2

−34.61

P38T106A

 

0.0027 ± 0.005

−33.43

P38T106G

 

0.0027 ± 0.005

−32.78

  1. aInteraction energies of 0 kcal/mol represent positive interaction energies