55

LAMPIRAN
Lampiran 1. Tabel Panjang Ikatan ETQ
No

Atom

19 - 20
19 - 5
5- 6
6-7
6-3
3-1
1-2
2-8
2-4
5-4
1-9
9 - 23
3 - 10
10 - 7
10 - 11
11 - 13
13 - 14
14 - 16
16 - 18
18 - 17
17 - 15
15 - 14
15 - 21
21 - 22
7 - 49
11 - 27

C-C
C-C
C-C
C-O
C-C
C-C
C-C
C - Cl
C-C
C-C
C-C
C-C
C-C
C-O
C-N
N-C
C-C
C-C
C-C
C-C
C-N
N-C
N- C
C-C
O-H
N-H

Panjang Ikatan ()
Experime
n
Hasil Docking
1.53
1.53
1.53
1.39
1.40
1.39
1.36
1.36
1.40
1.39
1.40
1.39
1.40
1.39
1.73
1.73
1.39
1.39
1.39
1.39
1.36
1.36
1.43
1.43
1.55
1.39
1.23
1.23
1.34
1.34
1.48
1.47
1.53
1.53
1.52
1.52
1.52
1.52
1.53
1.52
1.48
1.47
1.47
1.47
1.47
1.47
1.53
1.53
0.96
1
1.01
1

Selisih Experimen Hasil

Docking
0.00
0.14
0.01
0.00
0.01
0.01
0.01
0.00
0.00
0.00
0.00
0.00
0.16
0.00
0.00
0.01
0.00
0.00
0.00
0.01
0.01
0.00
0.00
0.00
-0.04
0.01

56

Lampiran 2. Tabel Sudut Ikat ETQ

no

Atom

22-21-15
21-15-17
17-15-14
15-17-18
17-18-16
18-14-14
15-14-16
15-14-13
16-14-13
14-13-11
13-11-16
11-10-12
12-10-3
10-3-6
6-3-1
1-3-5
3-5-19
5-19-20
5-19-20
5-4-2
4-2-8
4-2-1
8-2-1
3-1-2
3-1-9
2-1-9
1-9-23

C-C-N
C-N-C
C-N-C
N-C-C
C-C-C
C-C-C
N-C-C
N-C-C
C-C-C
C-C-N
C-N-C
N-C-C
O -C - C
C-C-C
C-C-C
C-C-C
O -C - C
C-C-C
C-C-C
C-C-C
C - C - Cl
C-C-C
Cl - C - C
C-C-C
C-C-O
C-C-O
C - O- C

Sudut ikat ()
Experimen Hasil Docking
110.4
111
108.2
109.5
107.7
104
106.5
104
102.9
104
102.1
104
105.6
104
110.2
111
109.5
109.5
111.2
109.5
123.6
122
123.6
124
120.6
121
119.1
120
119.1
120
119.9
115
118.9
115
124.0
120
111.6
109.5
120.5
120
119.6
120
120.5
120
119.8
120
119.8
120
121.1
115
119.1
115
108.7
109.5

Selisih Experimen hasil docking

-0.6
-1.3
3.7
2.5
-1.1
-1.9
1.6
-0.8
0.0
1.7
1.6
-0.4
-0.4
-0.9
-0.9
4.9
3.9
4.0
2.1
0.5
-0.4
0.5
-0.2
-0.2
6.1
4.1
-0.8

57

Lampiran 3. Tabel Muatan ETQ

Muatan
No.
Atom
Hasil
atom
Experimen Docking
1
C
0.012
0.012
2
C
0.094
0.094
3
C
0.109
0.109
4
C
-0.072
-0.072
5
C
0.051
0.051
6
C
-0.008
-0.008
7
O
-0.222
-0.222
8
Cl
-0.041
-0.041
9
O
-0.208
-0.208
10
C
0.035
0.356
11
N
-0.151
0.148
12
O
-0.522
-0.523
13
C
0.015
0.051
14
C
0.025
0.016
15
N
-0.299
0.008
16
C
-0.035
0.006
17
C
-0.001
-0.011
18
C
-0.039
0.002
19
C
0.028
0.028
20
C
-0.061
-0.061
21
C
-0.004
-0.014
22
C
-0.052
-0.016
23
C
0.05
0.119
+
24
H
-0.009
25
H
0.066
0.066
26
H
0.261
0.261
27
H
0.137
0.137
28
H
0.049
0.054
29
H
0.049
0.054
30
H
0.048
0.1
31
H
0.028
0.034
32
H
0.028
0.034
33
H
0.043
0.094
34
H
0.028
0.094
35
H
0.028
0.034

selisih experimen -docking

0
0
0
0
0
0
0
0
0
-0.321
-0.299
0.001
-0.036
0.009
-0.307
-0.041
0.01
-0.041
0
0
0.01
-0.036
-0.069
0.009
0
0
0
-0.005
-0.005
-0.052
-0.006
-0.006
-0.051
-0.066
-0.006

58

36
37
38
39
40
41
42
43
44
45
46
47
48
49

H
H
H
H
H
H
H
H
H
H
H
H
H
H

0.028
0.032
0.023
0.032
0.023
0.023
0.043
0.043
0.024
0.032
0.024
0.066
0.066
0.066

0.034
0.032
0.032
0.023
0.023
0.023
0.094
0.094
0.03
0.03
0.03
0.066
0.066
0.066

-0.006
0
-0.009
0.009
0
0
-0.051
-0.051
-0.006
0.002
-0.006
0
0
0

59

Lampiran 4. Tabel Panjang Ikatan Aripiprazole

no
Atom

Atom

30-4
22-3
16-3
16-15
15-13
13-12
30-25
25-20
20-19
19-21
19-28
28-29
29-22
22-26
26-21
21-7
30-7
31 - 7
12 - 5
5-9
5-8
8 - 10
11 - 9
11 - 6
6 - 10
14 - 6
14 - 18
18 - 24
24 - 27
27 - 23
23 - 17
23 - 2
17 - 1

C=O
C-O
C-O
C-C
C-C
C-C
C-C
C-C
C-C
C=C
C-C
C=C
C-C
C=C
C-C
C-N
C-N
H- N
C- N
N-C
N-C
C-C
C-C
C-N
N-C
C-N
C-C
C=C
C-C
C=C
C-C
C - Cl
C- Cl

Panjang Ikatan ( )
Hasil
Experimen
Docking
1.22
1.244
1.36
1.3804
1.43
1.435
1.54
1.5194
1.54
1.5126
1.54
1.5287
1.51379
1.5109
1.53497
1.5137
1.5196
1.4863
1.34644
1.4209
1.46511
1.3918
1.33929
1.3931
1.45865
1.4
1.33956
1.4041
1.46082
1.4067
1.32579
1.3982
1.32088
1.3913
1.01
0.99999
1.47
1.4472
1.47147
1.4495
1.47151
1.4494
1.5401
1.5447
1.54004
1.5457
1.46834
1.4566
1.46838
1.4541
1.32
1.4264
1.46002
1.409
1.34
1.3908
1.45997
1.3912
1.34
1.3976
1.46
1.403
1.76
1.6991
1.76
1.6967

Selisih
Experiment Docking
-0.024
-0.0204
-0.005
0.0206
0.0274
0.0113
0.00289
0.02127
0.0333
-0.07446
0.07331
-0.05381
0.05865
-0.06454
0.05412
-0.07241
-0.07042
0.01001
0.0228
0.02197
0.02211
-0.0046
-0.00566
0.01174
0.01428
-0.1064
0.05102
-0.0508
0.06877
-0.0576
0.057
0.0609
0.0633

60

Lampiran 5. Sudut Ikat Aripiprazole

No Atom
4 - 30 - 7
4 - 30 -25
31 - 7 - 30
31 - 7 - 21
7 - 21 -19
21 - 19 - 20
19-20-25
20 -25 - 53
21 -25 - 52
54 - 26 - 21
54 - 26 - 22
22-26-21
22 - 29 -28
19 - 28 - 29
19 - 28 - 56
28-29-57
22-3-16
3-22-26
3 -22 -29
3- 16 - 15
16-15-13
15-13-12
9-5-12
12 - 5 -8
8-10-6
9 -11 -6
14 - 6 - 11
14 - 6 - 10
17-14-6
18-14-6
24 - 18 -48
51-24-27
24 - 27 -55
27 -23 2

Atom
O-C-N
O-C-C
H-N-C
H-N-C
N-C=C
C=C-C
C-C-C
C-C-H
C-C-H
H-C -C
H-C=C
C=C-C
C-C=C
C=C-C
C-C-H
C=C-H
C-O-C
O-C=C
O-C-C
O -C - C
C-C-C
C-C-C
C-N-C
C-N-C
C-C-N
C-C-N
C-N-C
C-N-C
C = C -N
C = C -N
C=C-H
H-C-C
C-C-H
C = C - Cl

Sudut ()
Hasil
Experimen Docking
120.163
118.936
120.162
122.647
118.95
118.844
118.95
118.841
121.7
120.025
120.716
119.745
108.693
112.661
109.798
105.989
109.88
108.496
119.795
120.355
119.795
120.355
120.41
119.29
120
118.958
120.091
121.471
120.053
119.264
120
120.519
109.471
115.907
120
114.244
120
124.588
109.471
106.345
109.471
113.096
109.471
111.631
109.471
115.899
109.412
116.209
109.078
112.112
109.079
111.637
120.546
115.02
120.546
113.849
120
118.863
120
122.773
120
119.482
120
119.738
120
120.24
120
118.447

Selisih
Experimen Docking
1.227
-2.485
0.106
0.109
1.675
0.971
-3.968
3.809
1.384
-0.56
-0.56
1.12
1.042
-1.38
0.789
-0.519
-6.436
5.756
-4.588
3.126
-3.625
-2.16
-6.428
-6.797
-3.034
-2.558
5.526
6.697
1.137
-2.773
0.518
0.262
-0.24
1.553

61

14-17 -1
17-23-2
23-17-1

C = C - Cl
C - C - Cl
C - C - Cl

120
119.99
120

120.525
120.824
119.607

-0.525
-0.834
0.393

62

Lampiran 6. Tabel muatan aripiprazole

Muatan atom
selisih
No atom
Atom
Experimen Experimen Hasil Docking
Docking
1
Cl
-0.071
-0.065
-0.006
2
Cl
-0.073
-0.064
-0.009
3
O
-0.24
-0.197
-0.043
4
O
-0.476
-0.718
0.242
5
N
-0.301
-0.288
-0.013
6
N
-0.12
0.019
-0.139
7
N
-0.074
0.019
-0.093
8
C
0.011
0.116
-0.105
9
C
0.011
0.116
-0.105
10
C
0.016
0.116
-0.1
11
C
0.016
0.116
-0.1
12
C
-0.002
0.116
-0.118
13
C
-0.038
0.116
-0.154
14
C
0.006
0.117
-0.111
15
C
-0.026
0.116
-0.142
16
C
0.055
0.271
-0.216
17
C
0.006
-0.037
0.043
18
C
-0.057
-0.023
-0.034
19
C
-0.023
-0.037
0.014
20
C
-0.004
0.116
-0.12
21
C
0.015
0.117
-0.102
22
C
0.028
0.117
-0.089
23
C
0.01
-0.037
0.047
24
C
-0.053
-0.023
-0.03
25
C
0.01
0.116
-0.106
26
C
0.013
-0.022
0.035
27
C
-0.051
-0.023
-0.028
28
C
-0.019
-0.023
0.004
29
C
-0.015
-0.023
0.008
30
C
0.084
0.254
-0.17
31
H
0.159
-0.014
0.173
32
H
0.044
-0.02
0.064
33
H
0.044
-0.021
0.065
34
H
0.044
-0.021
0.065
35
H
0.044
-0.021
0.065

63

36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57

H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H

0.045
0.045
0.045
0.045
0.043
0.043
0.028
0.028
0.029
0.029
0.06
0.06
0.064
0.033
0.033
0.062
0.03
0.03
0.072
0.064
0.067
0.07

-0.021
-0.021
-0.021
-0.021
-0.021
-0.021
-0.021
-0.02
-0.021
-0.021
-0.021
-0.021
0.009
-0.021
-0.021
0.009
-0.021
-0.021
0.009
0.009
0.009
0.009

0.066
0.066
0.066
0.066
0.064
0.064
0.049
0.048
0.05
0.05
0.081
0.081
0.055
0.054
0.054
0.053
0.051
0.051
0.063
0.055
0.058
0.061

64

Lampiran 7. log file penambahan missing atom dan reconstructing sidechain

swisspdbviewer
/LOAD
PDB
log
file
for
A:\CIRUSS\lesson
to
be
chemist\TA\cobaswiss\3PBLchainb.pdb
/=====================================================
/loading layer 0
Missing Atom: OG for residue SER 145 of chain 'B'
Missing Atom: CG for residue ARG 149 of chain 'B'
Missing Atom: CD for residue ARG 149 of chain 'B'
Missing Atom: NE for residue ARG 149 of chain 'B'
Missing Atom: CZ for residue ARG 149 of chain 'B'
Missing Atom: NH1 for residue ARG 149 of chain 'B'
Missing Atom: NH2 for residue ARG 149 of chain 'B'
Missing Atom: CG for residue ASN 1040 of chain 'B'
Missing Atom: OD1 for residue ASN 1040 of chain 'B'
Missing Atom: ND2 for residue ASN 1040 of chain 'B'
Missing Atom: CG for residue ASN 1053 of chain 'B'
Missing Atom: OD1 for residue ASN 1053 of chain 'B'
Missing Atom: ND2 for residue ASN 1053 of chain 'B'
Missing Atom: CG for residue ASN 1055 of chain 'B'
Missing Atom: OD1 for residue ASN 1055 of chain 'B'
Missing Atom: ND2 for residue ASN 1055 of chain 'B'
Missing Atom: CG for residue ARG 1080 of chain 'B'
Missing Atom: CD for residue ARG 1080 of chain 'B'
Missing Atom: NE for residue ARG 1080 of chain 'B'
Missing Atom: CZ for residue ARG 1080 of chain 'B'
Missing Atom: NH1 for residue ARG 1080 of chain 'B'
Missing Atom: NH2 for residue ARG 1080 of chain 'B'
Reconstructing Sidechain of residue S 145 of chain 'B'
Reconstructing Sidechain of residue R 149 of chain 'B'
Reconstructing Sidechain of residue N 1040 of chain 'B'
Reconstructing Sidechain of residue N 1053 of chain 'B'
Reconstructing Sidechain of residue N 1055 of chain 'B'
Reconstructing Sidechain of residue R 1080 of chain 'B'
/done loading layer 0:3PBLchainb
/-------------------------------------------------------

65

Lampiran 8. File input protokol simulasi energi minimisasi steep descent

; Run control
integrator
= steep
nsteps
= 5000
; EM criteria and other stuff
emtol
= 100
emstep
= 0.01
niter
= 20
nbfgscorr
= 10
; Output control
nstlog
=1
nstenergy
=1
; Neighborsearching and short-range nonbonded interactions
nstlist
=1
ns_type
= grid
pbc
= xyz
rlist
=1
; Electrostatics
coulombtype
= PME
rcoulomb
= 1.0
; van der Waals
vdw-type
= switch
rvdw-switch
= 0.8
rvdw
= 0.9
; Apply long range dispersion corrections for Energy and Pressure
DispCorr
= EnerPres
; Spacing for the PME/PPPM FFT grid
fourierspacing
= 0.12
; EWALD/PME/PPPM parameters
pme_order
=6
ewald_rtol
= 1e-06
epsilon_surface
=0
optimize_fft
= no
; Temperature and pressure coupling are off during EM
tcoupl
= no
pcoupl
= no

66

Lampiran 9. File input protokol simulasi energi minimisasi L-BFGS

; Run control
integrator
= l-bfgs
nsteps
= 5000
define
= -DFLEXIBLE
; EM criteria and other stuff
emtol
= 100
emstep
= 0.01
niter
= 20
nbfgscorr
= 10
; Output control
nstlog
=1
nstenergy
=1
; Neighborsearching and short-range nonbonded interactions
nstlist
=1
ns_type
= grid
pbc
= xyz
rlist
= 1.0
; Electrostatics
coulombtype
= PME
rcoulomb
= 1.0
; van der Waals
vdw-type
= switch
rvdw-switch
= 0.8
rvdw
= 0.9
; Apply long range dispersion corrections for Energy and Pressure
DispCorr
= EnerPres
; Spacing for the PME/PPPM FFT grid
fourierspacing
= 0.12
; EWALD/PME/PPPM parameters
pme_order
=6
ewald_rtol
= 1e-06
epsilon_surface
=0
optimize_fft
= no
; Temperature and pressure coupling are off during EM
tcoupl
= no
pcoupl
= no

67

Lampiran 10. File input protokol simulasi kondisi NVT

title
= NVT equil
; Run parameters
integrator
= md
; leap-frog integrator
;nsteps
= 50000
; 2 * 50000 = 100 ps
nsteps
= 50000
; 2 * 500 = 1 ps
dt
= 0.002
; 2 fs
; Output control
nstxout
= 1000
; save coordinates every 0.2 ps
nstvout
= 1000
; save velocities every 0.2 ps
nstxtcout
= 1000
nstenergy
= 100
; save energies every 0.2 ps
nstlog
= 100
; update log file every 0.2 ps
; Bond parameters
continuation = no
; first dynamics run
constraint_algorithm = lincs ; holonomic constraints
constraints
= all-bonds ; all bonds (even heavy atom-H bonds) constrained
lincs_iter
=1
; accuracy of LINCS
lincs_order
=4
; also related to accuracy
; Neighborsearching
vdw_type
= cut-off
; search neighboring grid cells
nstlist
= 10
; 10 fs
rlist
= 1.0
; short-range neighborlist cutoff (in nm)
rcoulomb
= 1.0
; short-range electrostatic cutoff (in nm)
rvdw
= 1.0
; short-range van der Waals cutoff (in nm)
; Electrostatics
coulombtype = PME
; Particle Mesh Ewald for long-range electrostatics
pme_order
=4
; cubic interpolation
fourierspacing = 0.16
; grid spacing for FFT
; Temperature coupling is on
tcoupl
= V-rescale ; modified Berendsen thermostat
tc-grps
= system
; two coupling groups - more accurate
tau_t
= 0.2
; time constant, in ps
ref_t
= 300
; reference temperature, one for each group, in K
; Pressure coupling is off
pcoupl
= no
; no pressure coupling in NVT
; Periodic boundary conditions
pbc
= xyz
; 3-D PBC
; Dispersion correction
DispCorr
= EnerPres
; account for cut-off vdW scheme
; Velocity generation
gen_vel
= yes
; assign velocities from Maxwell distribution

68

gen_temp
gen_seed

= 300
= -1

; temperature for Maxwell distribution

; generate a random seed

69

Lampiran 11. File input protokol simulasi kondisi NPT

; Run parameters
integrator
= md
; leap-frog integrator
;nsteps
= 50000
; 2 * 50000 = 100 ps
nsteps
= 50000
; 2 * 500 = 1 ps
dt
= 0.002
; 2 fs
; Output control
nstxout
= 1000
; save coordinates every 0.2 ps
nstvout
= 1000
; save velocities every 0.2 ps
nstxtcout
= 1000
nstenergy
= 100
; save energies every 0.2 ps
nstlog
= 100
; update log file every 0.2 ps
; Bond parameters
continuation = yes
; Restarting after NVT
constraint_algorithm = lincs ; holonomic constraints
constraints
= all-bonds ; all bonds (even heavy atom-H bonds) constrained
lincs_iter
=1
; accuracy of LINCS
lincs_order
=4
; also related to accuracy
; Neighborsearching
ns_type
= grid
; search neighboring grid cells
nstlist
= 10
; 10 fs
rlist
= 1.0
; short-range neighborlist cutoff (in nm)
rcoulomb
= 1.0
; short-range electrostatic cutoff (in nm)
rvdw
= 1.0
; short-range van der Waals cutoff (in nm)
; Electrostatics
coulombtype = PME
; Particle Mesh Ewald for long-range electrostatics
pme_order
=4
; cubic interpolation
fourierspacing = 0.16
; grid spacing for FFT
; Temperature coupling is on
tcoupl
= V-rescale ; modified Berendsen thermostat
tc-grps
= system
; two coupling groups - more accurate
tau_t
= 0.2
; time constant, in ps
ref_t
= 300
; reference temperature, one for each group, in K
; Pressure coupling is on
pcoupl
= Parrinello-Rahman ; Pressure coupling on in NPT
pcoupltype
= isotropic
; uniform scaling of box vectors
tau_p
= 5.0
; time constant, in ps
ref_p
= 1.0
; reference pressure, in bar
compressibility = 4.5e-5
; isothermal compressibility of water, bar^-1
refcoord_scaling = com
; Periodic boundary conditions

69

pbc
= xyz
; Dispersion correction
DispCorr
= EnerPres
; Velocity generation
gen_vel
= no

; 3-D PBC
; account for cut-off vdW scheme
; Velocity generation is off

71

Lampiran 12. File input protokol simulasi perhitungan Free Energy

Pertubastion pembuatan lambda
; we'll use the sd integrator with 600000 time steps (1200ps)
integrator
= sd
nsteps
= 600000
dt
= 0.002
nstenergy
= 1000
nstlog
= 5000
; turn off trajectory writing
nstxout
= 1000
nstvout
= 1000
nstxtcout
= 1000
; We use the old group scheme because as of writing, the Verlet scheme
; does not support free energy calculations with coupled molecules.
cutoff-scheme
= group
; cut-offs at 1.0nm
rlist
= 1.0
dispcorr
= EnerPres
vdw-type
= cut-off
rvdw
=1
; Coulomb interactions
coulombtype
= pme
rcoulomb
= 1.0
fourierspacing
= 0.12
; Constraints
constraints
= all-bonds
; set temperature to 300K
tcoupl
= v-rescale
tc-grps
= system
tau-t
= 0.2
ref-t
= 300
; set pressure to 1 bar with a thermostat that gives a correct
; thermodynamic ensemble
pcoupl
= parrinello-rahman
ref-p
=1
compressibility
= 4.5e-5
tau-p
=5
; and set the free energy parameters
free-energy
= yes
couple-moltype
= PDB

71

; these 'soft-core' parameters make sure we never get overlapping

; charges as lambda goes to 0
sc-power
=1
sc-sigma
= 0.3
sc-alpha
= 1.0
; we still want the molecule to interact with itself at lambda=0
couple-intramol
= no
couple-lambda1
= vdwq
couple-lambda0
= none
init-lambda-state
= $LAMBDA$
fep-lambdas
= 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

71

Lampiran 13. Daftar singkatan asam amino

Alanin (Ala)
Arginin (Arg)
Asam aspartat (Asp)
Asam glutamat (Glu)
Asparagin (Asn)
Fenilalanin (Phe)
Glisin (Gly)
Glutamin (Gln)
Histidin (His)
Isoleusin (Ile)
Leusin (Leu)
Lisin (Lys)
Metionin (Met)
Prolin (Pro)
Serin (Ser)
Sistein (Cys)
Tirosin (Tyr)
Treonin (Thr)
Triptofan (Trp)
Valin (Val)