preparing new trypsin model

new trypsin model

1. Superposition

home/henricsn/combine2go/data/trypsin/pdb/
superimpose 1o2k to 1o5a
superimpose further trypsin structures to aligned 1o2k structure

2. Building a receptor model

selecting 1o2r (bovine trypsin) for trypsin model
removing alternative conformations and water molecules
trypsin-model-temp.pdb

/home/henricsn/combine2go/data/trypsin/pdb/model
xleap.sh -pdb trypsin-model -n 000 -prot trypsin-model-temp.pdb -lig model1.ligand -m /home/henricsn/combine2go/parameter/protmin.trypsin-model.template -w -noac -nopc -notemp -bres -noedit |tee xleap.log

/home/henricsn/combine2go/parameter/protmin.trypsin-model.template
model1.ligand (empty dummy file)
trypsin-model.min.pdb
trypsin-model.minbres.pdb
trypsin-model.top
trypsin-model.cor
trypsin-model.min.xyz

3. Ki values

checking Ki values
/home/henricsn/combine2go/sdf/all_151205_3D.sdf

4. Preparation of ligands

adding new structures
pconv -g -no -s 1o2k -pdb 1o3k -n A50

adding hydrogens with pymol and saving modified ligands as
/home/henricsn/combine2go/data/trypsin/pdb/ligand/*.ligand.prot.pdb

5. Minimization

start minimization in /home/henricsn/combine2go/data/trypsin/mod17_151205
local_start.sh -sdf /home/henricsn/combine2go/sdf/all_151205_3D.sdf -inrec ./ -inlig /home/henricsn/combine2go/data/trypsin/pdb/ligand/ -model trypsin.pdb -ligbase .ligand.prot.pdb |tee local.log

6. Interaction energies

start calculation of interaction energies
calc_inter_model.sh |tee calc.log

Changing from Ki values for human trypsin to bovine trypsin
using Ki for bovine trypsin (trypsin_bos)

start minimization in /home/henricsn/combine2go/data/trypsin/mod17_151205
local_start.sh -sdf /home/henricsn/combine2go/sdf/all_191205_3D.sdf -inrec ./ -inlig /home/henricsn/combine2go/data/trypsin/pdb/ -model trypsin.pdb -ligbase .ligand.prot.pdb |tee local2.log

Problems
antechamber is not working with netcharge -1!

new bovine trypsin model

Ki values for bovine trypsin@pHmin

Using Ki values from human trypsin together with bovine x-ray complexes gives negative q2 values!


 set1
 set2
 set3
 set4
 set5
 set6
 set7
 set8
 set9
 set10
 set11
 set12
1
 1
1
1
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1
 1
 1
 1
2
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2
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3
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3
3
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3
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4
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4
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5
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5
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5
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6
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6
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7











8
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8
8
8
 -
 x
 x
 x
9











10
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10
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11
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11
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13
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15
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20
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20
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r2
 0.8278

0.9980
 0.9767
 0.8884 (3)
0.8108 (2)
0.6961
 0.7724 0.7586
 0.6937
q2
 0.4539
 -
 -
 0.5493
 0.2550
 0.4719 (3)
0.3749 (2)
 -
 0.3211
 0.3511 0.1314
 0.2479
LV
 2

4
 5
 3/2
2
 2
 2
 2

final trypsin model (set6)
trypsin-model.dat.tar.gz
log-file

after variable selection (LV3)
Principal Component Analysis (PCA) 11 objects 85 X-var
components XVarExp XAccum
1 39.2675 39.2675
2 30.6999 69.9674
3 12.1012 82.0686
4 8.8232 90.8918
5 2.1353 93.0271

PCA Rank Validation - using 4 random groups
components PRESS Seps R
1 5.1968e+01 6.5337e+01 0.7954
2 3.5827e+01 3.5633e+01 1.0054
3 1.5925e+01 1.5628e+01 1.0189
4 5.2606e+00 8.1466e+00 0.6457
5 3.3621e+00 3.5390e+00 0.9500

Partial Least Squares (PLS) 11 objects 85 X-var 1 Y-var
Y1 components XVarExp XAccum SDEC r2
0 0.0000 0.0000 0.9557 0.0000
1 24.3708 24.3708 0.5000 0.7263
2 27.0035 51.3742 0.3478 0.8676
3 25.7237 77.0979 0.2123 0.9506
4 12.7091 89.8071 0.1812 0.9640
5 1.6435 91.4505 0.0963 0.9898

PLS Model Validation - LOO
Y1 components SDEP SDEV(sdep) q2
0 1.0512 - -0.2100
1 0.7711 - 0.3490
2 0.5793 - 0.6326
3 0.4598 - 0.7685
4 0.3986 - 0.8260
5 0.4613 - 0.7670


set6 without variable selection
External PLS predictions for /home/henricsn/combine2go/data/trypsin/mod17_151205/golpe-bos/output.dat

1 A13.0
Exper: -8.073 Pred:( 1 ) -7.907 ( 2 ) -7.437 ( 3 ) -7.642 ( 4 ) -8.14 ( 5 ) -8.084

2 A12.0
Exper: -7.456 Pred:( 1 ) -8.436 ( 2 ) -7.896 ( 3 ) -7.967 ( 4 ) -7.617 ( 5 ) -7.446

3 A18.0
Exper: -9.544 Pred:( 1 ) -9.162 ( 2 ) -9.571 ( 3 ) -9.158 ( 4 ) -9.312 ( 5 ) -9.357

4 A15.0
Exper: -9.931 Pred:( 1 ) -9.812 ( 2 ) -9.443 ( 3 ) -9.693 ( 4 ) -9.71 ( 5 ) -9.966

5 A01.0
Exper: -9.436 Pred:( 1 ) -9.804 ( 2 ) -9.482 ( 3 ) -9.543 ( 4 ) -9.492 ( 5 ) -9.488

6 A16.0
Exper: -8.667 Pred:( 1 ) -9.027 ( 2 ) -9.443 ( 3 ) -9.139 ( 4 ) -9.111 ( 5 ) -8.89

7 A06.0
Exper: +8.889e+05 Pred:( 1 ) -8.851 ( 2 ) -9.115 ( 3 ) -8.642 ( 4 ) -8.526 ( 5 ) -8.588

8 A11.0
Exper: -10.47 Pred:( 1 ) -8.751 ( 2 ) -8.574 ( 3 ) -8.047 ( 4 ) -8.302 ( 5 ) -8.458

9 A17.0
Exper: +8.889e+05 Pred:( 1 ) -9.074 ( 2 ) -9.364 ( 3 ) -9.029 ( 4 ) -9.404 ( 5 ) -9.541

10 A09.0
Exper: -7.833 Pred:( 1 ) -7.822 ( 2 ) -7.957 ( 3 ) -8.012 ( 4 ) -7.769 ( 5 ) -7.727

11 A03.0
Exper: -9.304 Pred:( 1 ) -9.316 ( 2 ) -10.04 ( 3 ) -10.18 ( 4 ) -10.26 ( 5 ) -10.43

12 A14.0
Exper: -9.722 Pred:( 1 ) -9.622 ( 2 ) -9.848 ( 3 ) -10.04 ( 4 ) -9.677 ( 5 ) -9.664

13 A04.0
Exper: -10.85 Pred:( 1 ) -9.632 ( 2 ) -9.875 ( 3 ) -9.931 ( 4 ) -9.262 ( 5 ) -8.999

14 A10.0
Exper: +8.889e+05 Pred:( 1 ) -8.502 ( 2 ) -9.102 ( 3 ) -9.3 ( 4 ) -9.203 ( 5 ) -9.466

15 A50.0
Exper: -9.23 Pred:( 1 ) -8.219 ( 2 ) -8.902 ( 3 ) -9.019 ( 4 ) -9.018 ( 5 ) -9.326

16 A52.0
Exper: +8.889e+05 Pred:( 1 ) -8.538 ( 2 ) -8.316 ( 3 ) -8.324 ( 4 ) -8.44 ( 5 ) -8.39

17 A53.0
Exper: -9.955 Pred:( 1 ) -8.381 ( 2 ) -8.836 ( 3 ) -8.956 ( 4 ) -8.927 ( 5 ) -9.174

18 A54.0
Exper: -10.71 Pred:( 1 ) -9.864 ( 2 ) -10.27 ( 3 ) -10.55 ( 4 ) -10.87 ( 5 ) -10.65

19 A55.0
Exper: +8.889e+05 Pred:( 1 ) -8.438 ( 2 ) -7.84 ( 3 ) -7.945 ( 4 ) -7.617 ( 5 ) -7.554

20 A56.0
Exper: -8.483 Pred:( 1 ) -8.232 ( 2 ) -7.764 ( 3 ) -7.863 ( 4 ) -7.92 ( 5 ) -7.924

21 A57.0
Exper: -8.305 Pred:( 1 ) -9.232 ( 2 ) -8.661 ( 3 ) -8.142 ( 4 ) -8.193 ( 5 ) -8.307


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