Department of Civil Engineering, College of Engineering
National Taiwan University Master Thesis
Binding Ability of Normal and Citrullinated Collagen with Integrins:A Molecular Dynamics Approach
Kao, Tsu-Hsin
:
Advisor: Shu-Wei Chang, Ph. D
109 12
November, 2020
國立臺灣大學碩士學位論文 口試委員會審定書
以分子動力模擬探討正常及瓜胺酸化膠原蛋白與整合素的結合力 Binding Ability of Normal and Citrullinated Collagen with
Integrins:A Molecular Dynamics Approach
本論文係高紫欣君 (R06521221) 在國立臺灣大學土木工程學系 完成之碩士學位論 文 ， 於民國 109 年 12 月 4 日承下列考試委員 審查通過及口試及格 ， 特此證明
口試委員：
張書瑋
（指導教授）徐駿森
}1] 白
竺汀汀
滸濟華 缢縐平
系 主 任
謝尚賢
..
＇ur:r A:l ,•
.
-
GLOGER GLOGER
GAOGER GAOGER
GLOGER Cit12C
E220 E11D
Cit12C
Cit12B E298 E255 Cit12C
D259 E11D R218
0 E11D R219
Abstract
Rheumatoid arthritis is an autoimmune disease that can cause repetitive inflammation of joints throughout the body, which can destroy and deform the cartilage or hard bones in the joints over a long period of time. According to recent studies, the synovial fluid extracted from the joint cavity of patients with rheumatoid arthritis or general osteoarthritis has discovered the autoantigens of rheumatoid arthritis-citrullinated type II and type III collagen. It has been proved to be closely related to the pathogenic mechanism of arthritis. More studies have found that synovial fibroblasts secrete related factors that promote inflammation and are considered to be key therapeutic targets;
integrins and are considered important because they can regulate their attachment and migration cell membrane receptor protein. Summarizing the above findings, it is very important to understand the effect of citrulline on the binding of collagen to the four integrins.
Although many studies have confirmed that citrulline is related to the mechanism of inflammation, it is still not clear how citrulline affects the binding of collagen to the four integrins. Therefore, this study will use molecular dynamics simulation to explore the normal GLOGER on a microscopic scale. The structural difference after combining with citrullinated GLOGER and integrin and as well as the structural difference between normal GAOGER and citrullinated GAOGER and integrin to explain the binding strength in the experimental data Influence and provide direction for future inflammation-related drug design.
This study found that citrulline acidification would greatly weaken the hydrogen bond between GLOGER and so that the side chain of Cit12C and E220 no longer generate hydrogen bonds, and even E11D no longer generates hydrogen bonds with resulting in almost loss of hydrogen bonds. The other three have their own mechanisms to alleviate citrulline acidification. For example, the main chain of Cit12Cstill maintains hydrogen bonds with the mechanism of is as follows. Although citrulline acidification prevents Cit12Bfrom forming hydrogen bonds with E298 and E255, the side chain of Cit12C is biased. It creates a new hydrogen bond with D259, and E11D and R218 still maintain the hydrogen bond, alleviating the effect of citrulline acidification; uses E11D and R219 to generate stronger hydrogen bonds. These important findings explain the different responses of citrulline to the binding of collagen to the four integrins, and also provide a reasonable explanation for future experimental data comparison.
Keywords: citrulline, collagen, integrin, molecular dynamics simulation, arthritis
... I Abstract III
... V ... IX ... XXI
... 1
1.1 ... 1
1.2 ... 10
1.3 ... 11
... 13
2.1 GFOGER R12C E11D F8B ... 13
2.1.1 GFOGER ... 13
2.1.2 GFOGER R12C E11D... 14
2.1.3 GFOGER F8B... 16
2.1.3.1 GFOGER F8B ... 16
2.1.3.2 GFOGER F8B ... 17
2.2 GLOGER ... 18
2.3 GAOGER ... 19
2.4 GFOGER Cit12C E11D ... 20
2.4.1 GFOGER ... 20
2.1.2 GFOGER Cit12C E11D... 20
2.5 GAOGER ... 22
... 23
3.1 ... 23
3.1.1 ... 23
3.1.2 ... 24
3.1.3 ... 24
3.2 ... 25
3.2.1 Topology File of Citrullination ... 25
3.2.2 Parameter File of Citrullination ... 27
3.2.2.1 Parameter File of Citrullination-Bonds... 27
3.2.2.2 Parameter File of Citrullination-Angles ... 27
3.2.2.3 Parameter File of Citrullination-Dihedrals ... 28
3.2.2.4 Parameter File of Citrullination-Impropers ... 30
3.3 ... 31
3.4 ... 32
3.5 ... 32
3.5.1 - ... 33
3.5.2 - ... 34
3.5.3 - - stacking ... 35
... 37
4.1 GFOGER ... 37
4.1.1 GFOGER ... 37
4.1.1.1 GFOGER R12B R12C ... 38
4.1.1.2 GFOGER E11C E11D... 47
4.1.2 GFOGER ... 52
4.1.3 GFOGER PI-stacking ... 55
4.1.4 GFOGER ... 57
4.2 GLOGER ... 59
4.2.1 GLOGER ... 59
4.2.1.1 GLOGER R12B... 59
4.2.1.2 GLOGER R12C E11D... 61
4.2.2 GLOGER ... 67
4.2.3 GLOGER ... 69
4.3 GAOGER ... 70
4.3.1 GAOGER ... 70
4.3.2 GAOGER A8B PI-stacking ... 71
4.3.3 GAOGER ... 72
... 73
5.1 GFOGER ... 73
5.1.1 GFOGER ... 74
5.1.2 GFOGER ... 84
5.1.3 GFOGER PI-stacking ... 86
5.1.4 GFOGER ... 88
5.2 GLOGER ... 89
5.2.1 GLOGER ... 89
5.2.2 GLOGER ... 95
5.2.3 GLOGER ... 97
5.3 GAOGER ... 98
5.3.1 GAOGER ... 98
5.3.2 GAOGER PI-stacking ... 100
5.3.3 GFOGER GLOGER GAOGER ... 101
... 103
6.1 ... 103
6.1.1 GFOGER... 103
6.1.2 GLOGER&GAOGER ... 104
6.1.3 GFOGER ... 105
6.1.4 GLOGER&GAOGER ... 106
6.2 ... 107
109
1. 1 Integrin integrin integrin [24,25]
... 3
1. 2 GFOGER GLOGER GFOGER
GAOGER [29,30] ... 4 1. 3 [1] ... 5
1. 4 PAD2 [5]
(
GFOGER ... 6
1. 5 GFOGER GFOGER
[5] ... 6
1. 6 integrin
[33] ... 6
1. 7 PAD4
integrin GLOGER
[35] ... 8
1. 8 PAD2 GFOGER GLOGER
GAOGER [36] ... 8 1. 9
GAOGER PAD2
[3,38] ... 9
2. 1 GFOGER ( [31]13 2. 2 254-258 ... 15
2. 3 B Arg E256 S257
H258 R12B
256 257 258 ... 15
2. 4 C Arg 189 219 220 222 190
R12C
... 15 2. 5 D219( R218( R219(
... 17 2. 6 B Phe
... 17
2. 7 GFOGER GLOGER [39] ... 18
2. 8 GFOGER [31] ... 18
2. 9 GFOGER GLOGER GAOGER GST
... 19
2. 10 GFOGER GFOGER (
... 21
2. 11 C Cit 189 219 220 222 190
... 21
2. 12 GAOGER
... 22
3. 1 [42] ... 24
3. 2 [42]... 25
3. 3 Cit Atom name ... 25
3. 4 Cit Atom type ... 26
3. 5 Cit Atom type Atom name- ... 27
3. 6 Cit Atom type Atom name- ... 27
3. 7 Cit Atom type Atom name- ... 28
3. 8 Cit Atom type Atom name- ... 29
3. 9 Cit Atom type Atom name- ... 30
3. 10 ... 32
3. 11 [51] ... 32
3. 12 [51] ... 33
3. 13 [51] ... 34
3. 14 - stacking [51] ... 35
3. 15 Sandwich T-shape L-shape ... 35
3. 16 - stacking
7.5 0°< <30° 60°< <120°[53] ... 35 4. 1 Backbone of 2I- ... 37
4. 3 B C D GFOGER NH+
Mg2+ 10.2~20.2ns ... 38 4. 4 NH+ ... 38
B C D GFOGER NH+ Mg2+
10.2~20.2ns ... 38
4. 5 B C D GFOGER ... 39
4. 6 R12B 10.2~20.2ns
... 40
B Arg (
B Arg (
E256 S257 ... 41
4. 7 B Arg ... 41
B Arg E256 S257 H258
10.2~20.2ns ... 41
4. 8 R12C 10.2~20.2ns
... 42
4. 10 R12C ... 43
4. 11 R12C 1 10.2~20.2ns . 44
R12 1 10.2~20.2ns ... 44
4. 12 R12C 10 10.2~20.2ns 45 R12C 10 10.2~20.2ns ... 45 4. 14 R12C 11 10.2~20.2ns ... 46
4. 15 C Glu OE1 Mg2+
10.2~20.2ns ... 47
4. 16 C Glu OE1 Mg2+
10.2~20.2ns ... 47
4. 17 C Glu OE1 Mg2+
... 48
4. 18 E11D 1 2 0 1 10.2~20.2ns ... 49
4. 2 E11D 0 1 10.2~20.2ns ... 49
4. 19 E11D 0 1
10.2~20.2ns ... 49
4. 20 E11D 0 1 10.2~20.2ns ... 50
4. 21 R12B R12C E11D 10.2~20.2ns
[31] ... 51 4. 22 Phe ... 52
4. 23 B C D GFOGER Phe CZ
Mg2+ 10.2~20.2ns ... 52 4. 24 F8B
10.2~20.2ns ... 53
4. 25 F8B 10.2~20.2ns( :
Y157 ... 54
4. 26 F8B PI-stacking 10.2~20.2ns ... 55
4. 27 F8B PI-stacking 10.2~20.2ns( : Y157 PI-stacking ... 56
4. 28 R12B R12C E11D 10.2~20.2ns [31] ... 57
4. 29 F8B 10.2~20.2ns [31] ... 58
4. 30 F8B PI-stacking 10.2~20.2ns [31] ... 58
4. 31 R12C 10.2~20.2ns ... 60
4. 32 R12C 10.2~20.2ns ... 62
R12C 10.2~20.2ns ... 62
4. 33 R12C 1 10.2~20.2ns ... 63
R12C 1 10.2~20.2ns ... 63
4. 34 R12C 10 10.2~20.2ns ... 64
R12C 10 10.2~20.2ns ... 64
4. 35 R12 11 10.2~20.2ns ... 65
R12C 11 10.2~20.2ns ... 65 4. 36 GLOGER R12B R12C E11D
10.2~20.2ns [39] ... 66
4. 37 GFOGER (
[31] ... 66
4. 38 L8B 10.2~20.2ns( :
Y157 ... 68
4. 39 GFOGER 10.2~20.2ns
[39] ... 69
4. 40 GLOGER 10.2~20.2ns
[39] ... 69
4. 41 R12B R12C E11D 10.2~20.2ns ... 70
4. 42 GFOGER GLOGER GAOGER
10.2~20.2ns ... 71
4. 43 GFOGER GLOGER GAOGER PI-stacking
10.2~20.2ns( : Y157 PI-stacking ... 71 4. 44 A8B 10.2~20.2ns ... 71
4. 45 R12B R12C E11D 10.2~20.2ns
[30] ... 72
4. 46 GFOGER GLOGER GAOGER PI-stacking
10.2~20.2ns ... 72
5. 1 Backbone of 2I- ... 73
5. 2 R12B R12C E11D
10.2~20.2ns ... 75
5. 3 R12C Cit12C
10.2~20.2ns ... 75
5. 4 R12C Cit12C 10.2~20.2ns
... 76
5. 5 R12C Cit12C
10.2~20.2ns ... 77
5. 6 R12C Cit12C 10.2~20.2ns
... 78
5. 7 Cit12C E11D [5] ... 78
5. 8 R12C Cit12C
10.2~20.2ns ... 79
5. 9 R12C Cit12C
10.2~20.2ns ... 80
5. 10 Cit12C E11D 10 [5] ... 80
5. 11 R12C Cit12C
10.2~20.2ns ... 81
5. 12 R12C Cit12C
10.2~20.2ns ... 82
5. 13 Cit12C E11D 11 [5] ... 82
5. 14 GFOGER GFOGER
( [5] ... 83
5. 15 Cit12B Cit12C E11D
10.2~20.2ns ... 83
5. 16 GFOGER
10.2~20.2ns ... 84
5. 17 GFOGER F8B
10.2~20.2ns( : Y157 ... 85
5. 18 GFOGER PI-stacking
10.2~20.2ns ... 86
5. 19 GFOGER F8B
PI-stacking 10.2~20.2ns( : Y157 PI-stacking ... 87
5. 20 Cit12B Cit12C E11D
10.2~20.2ns ... 88
5. 21 GFOGER
10.2~20.2ns ... 88
5. 22 GFOGER PI-stacking
10.2~20.2ns ... 88
5. 23 GFOGER (
[5] ... 88
5. 24 Cit12B Cit12C E11D
10.2~20.2ns ... 90
5. 25 R12C Cit12C
10.2~20.2ns ... 91
5. 26 R12C Cit12C 10.2~20.2ns . 91
5. 27 R12C Cit12C
10.2~20.2ns ... 92
5. 28 R12C Cit12C 10.2~20.2ns . 92
5. 29 R12C Cit12C
10.2~20.2ns ... 93
5. 30 R12C Cit12C 10.2~20.2ns
... 93
5. 31 R12C Cit12C
10.2~20.2ns ... 94
5. 32 R12C Cit12C 10.2~20.2ns 94
5. 33 GLOGER
10.2~20.2ns ... 95
5. 34 GLOGER L8B
10.2~20.2ns( : Y157 ... 96
5. 35 Cit12B Cit12C E11D
10.2~20.2ns ... 97
GLOGER
10.2~20.2ns ... 97
5. 36 GFOGER GLOGER GAOGER Cit12B Cit12C
E11D 10.2~20.2ns ... 98
5. 37 GFOGER GLOGER GAOGER
10.2~20.2ns ... 100
5. 38 GFOGER PI-stacking
10.2~20.2ns ... 100
5. 39 GAOGER A8B 10.2~20.2ns
... 100
5. 40 GFOGER GLOGER GAOGER Cit12B Cit12C
E11D 10.2~20.2ns ... 101
5. 41 GFOGER GLOGER GAOGER
10.2~20.2ns ... 101
5. 42 GFOGER PI-stacking
10.2~20.2ns ... 101
5. 43 GAOGER
[3] ... 101
1. 1 integrin [31] ... 4 3. 1 Cit ... 26 3. 2 Cit ... 27 3. 3 Cit ... 27 3. 4 Cit ... 28 3. 5 Cit ... 29
3. 6 Cit ... 30
3. 7 20 [52] ... 33 4. 2 GLOGER R12B
10.2~20.2ns ... 59 4. 3 GFOGER R12B
10.2~20.2ns ... 59
4. 4 GLOGER R12C E11D 10.2~20.2ns
... 61
4. 5 GFOGER R12C E11D 10.2~20.2ns
... 61
4. 6 L8B 10.2~20.2ns
... 67
4. 7 F8B 10.2~20.2ns
... 67 4. 8 R12B R12C E11D 10.2~20.2ns ... 70
5. 1 R12B R12C E11D
10.2~20.2ns ... 74
5. 2 GFOGER
10.2~20.2ns ... 84
5. 3 GFOGER PI-stacking
10.2~20.2ns ... 86
5. 4 Cit12B Cit12C E11D
10.2~20.2ns ... 90
5. 5 GLOGER
10.2~20.2ns ... 95
5. 6 GFOGER GLOGER GAOGER Cit12B Cit12C
E11D 10.2~20.2ns ... 99
1.1
[1]
[2]
- (citrullinated type II&III
[3,4]
0
[5] 0
1/3[6]
[7] 20
[8]
[9,10,11,12]
[13] 16
[14]
[15] (chondrocyte
[16] [17]
[18]
[19,20]
[21]
[22]
[23]
1. 1 Integrin integrin integrin [24,25]
GFOGER(O Hydroxyproline GLOGER[26,27,28]
GFOGER GLOGER[29] GFOGER GLOGER
GAOGER[3]
GFOGER
GLOGER GFOGER GAOGER [30]
1. 1 integrin [31]
1. 2 GFOGER GLOGER GFOGER
GAOGER [29,30]
(post-translational modification (peptidylarginine deiminase
[32,1] [3]
40 (8 32
GFOGER
[5]
(P. gingivalis
[33]
[33]
[34]
1. 3 [1]
1. 4 PAD2 [5]
( GFOGER
1. 5 GFOGER GFOGER
[5]
1. 6 integrin
[33]
GLOGER [35]
GFOGER GLOGER GAOGER [36]
GAOGER [37]
GFOGER[5]
GLOGER GAOGER
1. 7 PAD4
integrin GLOGER
[35]
1. 8 PAD2 GFOGER GLOGER
GAOGER [36]
1. 9
GAOGER PAD2
[3,38]
1.2
GLOGER 0 GAOGER
1.3
GFOGER GFOGER
GLOGER
GAOGER GAOGER
- stacking
GFOGER
PI-stacking GFOGER
GLOGER
GLOGER GAOGER
GAOGER
GFOGER PI-
stacking GFOGER
GLOGER
GLOGER GAOGER
GAOGER
2.1 GFOGER
R12
CE11
DF8
B2.1.1 GFOGER
GFOGER (
GFOGER
0 [31]
2. 1 GFOGER ( 10 [31]
1.45
:1.5 105cells/ml
2.1.2 GFOGER R12
CE11
D[5] (cell
GFOGER
2 GFOGER 1dzi[44] Protein
Data Bank[45]
SWISS-PROT[46] BODIL[53] 2 52.3%(
45.7%( 46.2%( Sybyl[48]
BODIL rotamer
R12D
R12D R12B R12C R12B MIDAS
R12C MIDAS B
Arg C Arg
B Arg E256 S257
H258 R12B
256 257 258
C Arg 189 219 220 222 190
R12C (unconserved
R12C N189 D219 L220
N222 N190
E188 N189 Q219 :
0 E189 E220 R12C K222
E189 E220 R222 R12C
C Glu Mg2+ D Glu R218 R219
2. 2 254-258
2. 3 B Arg E256 S257
H258 R12B
256 257 258
2. 4 C Arg 189 219 220 222 190
R12C
254 255 256 257 258
D G E S H
253 254 255 256 257
D G E S H
254 255 256 257 258
D G E S H
252 253 254 255 256
D G E S H
A2 A1 A10 A11
189 190
N N
219 220 221 222
D L T N
188 189
E N
218 219 220 221
R Q T M
189 190
E S
219 220 221 222
R E T K
189 190
E D
219 220 221 222
T E T R
A10
A11 A2
A1
2.1.3 GFOGER F8
B[39] GFOGER 2 1
2 GFOGER 1dzi[44]
Protein Data Bank[45] SWISS-
PROT[46] BODIL[53] GFO
B Phe Phe
Leu Ala
GER Mg2+ Glu
D219( R218( R219(
0 0
219 Arg
2.1.3.1 GFOGER F8B
F8D F8D
F8B F8C F8B MIDAS
F8C MIDAS B Phe C
Phe
C Phe N154 C
Phe Leu Ala
B Phe :
F8B Y157 (aromatic
in -
F8B L286 F8B Y285
B Phe Leu Y285
B Phe
Ala
2.1.3.2 GFOGER F8B
154
F8C N154
B Phe Leu 1
2. 5 D219( R218( R219(
2. 6 B Phe
2.2 GLOGER
[39] GLOGER GST
1
[31] GLOGER (
GLOGER- GFOGER- GLOGER
GFOGER
(2500kcps 2500kcps 2 GLOGER(3100
kcps 1400kcps GFOGER(3900kcps 2650kcps
GLOGER
2. 7 GFOGER GLOGER [39]
2. 8 GFOGER [31]
2.3 GAOGER
[29,39] GFOGER GLOGER GAOGER
2. 9 GFOGER(3900kcps 0kcps
GAOGER(600kcps 2. 9
GFOGER GLOGER
GAOGER
2. 9 GFOGER GLOGER GAOGER GST
3.5
2.4 GFOGER
Cit12
CE11
D2.4.1 GFOGER
GFOGER
[5]
GFOGER (Chinese hamster ovary CHO
: :
0: 50% :
68%
a10 a11 50%
40% a1 a2 a1 a2
2.1.2 GFOGER Cit12
CE11
DB Cit 256 257 258
Cit12B R12B
C Cit
Cit12C
D219 Cit12C NE NH2 N189
ND2 Cit12C Cit12C
E11D R218
Cit12C :
E189
E220 Cit12C K222
(N189 Q219 2(N189 L220 E189 E220
Cit12C Cit12C R222
E189 E220 Cit12C R222
2. 10 GFOGER GFOGER (
2. 11 C Cit 189 219 220 222 190
2.5 GAOGER
[3]
(n
GAOGER
GAOGER
2. 12 GAOGER
3.1
3.1.1
[41] [54]
= = ( )
=
=
i m i m
( ) N
3.1.2
( ) = (r), r 0, >
(r) ( )
3.1.3
[42]
:
E = ( )
+ ( )
+ [1 + cos( )]
+ ( ) + 2 +
4
3. 1
[42]
3. 2 [42]
3.2
3.2.1 Topology File of Citrullination
CHARMM22All-Hydrogen Topology and Parameter File for Proteins[43]
SwissSidechain Topology and Parameter File for Non-natural sidechains [44]
3. 3 Cit Atom name
3. 4 Cit Atom type
3. 1 Cit
Atom name Atom Type Charge
1 N NH1 -0.470
2 HN H 0.310
3 CA CT1 0.070
4 HA HB 0.090
5 CB CT2 -0.180
6 HB1 HA 0.090
7 HB2 HA 0.090
8 CG CT2 -0.180
9 HG2 HA 0.090
10 HG1 HA 0.090
11 CD CT2 0.120
12 HD1 HA 0.090
13 HD2 HA 0.090
14 NE NH1 -0.730
15 HE H 0.370
16 CZ CC 0.630
17 OH O -0.570
18 NH NH2 -0.620
19 HH1 H 0.300
20 HH2 H 0.320
21 C C 0.510
22 O O -0.510
3.2.2 Parameter File of Citrullination
3.2.2.1 Parameter File of Citrullination-Bonds3. 5 Cit Atom type Atom name-
3. 2 Cit
3.2.2.2 Parameter File of Citrullination-Angles
3. 6 Cit Atom type Atom name-
3. 3 Cit
NH1 CC
NE CZ
BOND atom type
atom name Kb b0
419.491 1.369
CT2 NH1 CC
CD NE CZ
H NH1 CC
HE NE CZ
NH1 CC O
NE CZ OH
NH1 CC NH2
NE CZ NH 116.009 114.923
59.084 119.600 41.380 120.277 65.273 127.152
Ktheta Theta0 Kub S0
atom type atom name
ANGLE
3.2.2.3 Parameter File of Citrullination-Dihedrals
3. 7 Cit Atom type Atom name-
3. 4 Cit
CT2 CT2 NH1 CC
CG CD NE CZ
CT2 CT2 NH1 CC
CG CD NE CZ
CT2 CT2 NH1 CC
CG CD NE CZ
CT2 NH1 CC NH2
CD NE CZ NH
CT2 NH1 CC O
CD NE CZ OH
CT2 NH1 CC O
CD NE CZ OH
CT2 NH1 CC O
CD NE CZ OH
CC NH1 CT2 HA
CZ NE CD HD1/2
CC NH1 CT2 HA
CZ NE CD HD1/2
CC NH1 CT2 HA
CZ NE CD HD1/2
atom type atom name
DIHEDRAL
Kchi n delta
-0.513 1 0.00
3.000 2 180.00
0.474 3 0.00
-0.073 3 0.00
-0.160 1 0.00
0.347 2 180.00
0.011 3 0.00
0.681 2 180.00 3.147 2 180.00
-1.050 1 0.00
3. 8 Cit Atom type Atom name-
3. 5 Cit
NH1 CC NH2 H
NE CZ NH HH1/2
NH1 CC NH2 H
NE CZ NH HH1/2
NH2 CC NH1 H
NH CZ NE HE
NH2 CC NH1 H
NH CZ NE HE
O CC NH1 H
OH CZ NE HE
O CC NH1 H
OH CZ NE HE
O CC NH1 H
OH CZ NE HE
0.00
0.00
180.00 DIHEDRAL
atom type
Kchi n delta
atom name
-0.227
0.718
2.487
3
1
2
0.645 3 0.00
1.748 2 180.00 0.645
1.748
3
2
0.00
180.00
3.2.2.4 Parameter File of Citrullination-Impropers
3. 9 Cit Atom type Atom name-
3. 6 Cit
NH1 H CC CT2
NE HE CZ CD
CC NH2 O NH1
CZ NH OH NE
NH2 H H CC
NH HH1 HH2 CZ 4.0000 0 0.00
20.0000 0 0.00
7.8291 0 0.00
IMPROPER atom type
Kpsi n psi0
atom name
3.3
2 GFOGER 1dzi[45] Protein Data Bank[46] (
GFOGER GPOGPOGFOGERGPOGPOGPO B
C D (P56199 169-353 0(O75578 164-
1(P61622 161-343 SWISS-PROT[47]
VMD[48] 2 52.3%( 45.7%( 46.2%(
0
1 238 239
GLOGER GAOGER GFOGER Phe
Leu Ala GFOGER GLOGER GAOGER
Arg Cit GFOGECit GLOGECit GAOGECit
4.1 2
GFOGER 1 GFOGER 10 GFOGER 11 GFOGER
4.2 2 GLOGER 1
GLOGER 10 GLOGER 11 GLOGER
4.3 2 GAOGER
5.1 2
GFOGECit 1 GFOGECit 10 GFOGECit
11 GFOGECit 5.2 2
GLOGECit 1 GLOGECit 10
GLOGECit 11 GLOGECit 5.3
2 GAOGER
3.4
3. 10
3.5
3.
11 - stacking [50,51]
3. 11 [51]
3.5.1 -
- ( aliphatic
( Ala Leu Ile Val ( Phe Tyr Trp
(
Met Ala Leu Ile
Val
4
3. 12 [51]
3. 7 20 [52]
3.5.2 -
( (
F O N F O N (
- -( 30 3
3. 13 [51]
3.5.3 - - stacking
- stacking
DNA -
stacking Sandwich T-shape L-shape
- stacking
7.5 0°< <30° 60°< <120° - stacking
3. 14 - stacking [51]
3. 15 Sandwich T-shape L-shape
3. 16 - stacking
7.5 0°< <30° 60°< <120°[53]
4.1 GFOGER
4. 1 Backbone of I-GFOGER complex
4.1.1 GFOGER
4. 2 GFOGER 1 2 10 11 10.2~20.2ns
4.1.1.1 GFOGER R12B R12C
GFOGER NH+
Mg2+ Arg
4. 1 B C D GFOGER NH+
Mg2+ 10.2~20.2ns GFOGER
D Arg
B Arg C Arg
4. 3 B C D GFOGER NH+
Mg2+ 10.2~20.2ns
4. 4 NH+
B C D GFOGER NH+ Mg2+
10.2~20.2ns
( 4. 3 3D ( 4. 3
D Arg
B Arg C Arg
4. 5 B C D GFOGER
(1) GFOGER R12B
B Arg
B Arg
4. 4 1 4. 4
R12B S257 R12B
D257 0 R12B H258
R12B E255
B Arg
E256 S257
H258
4. 6 R12B 10.2~20.2ns
B Arg ( 4. 5
B Arg ( 4. 5
E256 S257
4. 7 B Arg
B Arg E256 S257 H258
10.2~20.2ns
(2) GFOGER R12C
C Arg
GFOGER
( 4. 6
( 4. 6 R12 D219
R12 T219 E220 E189 R12 R218
R12 E220
4. 8 R12C 10.2~20.2ns
R12C R12C H258 D219
2.86 R12C H258 H258
R12C R12C
D219 R12C D219
R12C N189 D219 L220
N222 N190
4. 9 R12C 10.2~20.2ns
4. 10 R12C
R12C R12C R218 0.48
R12C R218 R12C
R218
R12C E189 R218 Q219 M221 N189
4. 11 R12C 1 10.2~20.2ns
R12C 1 10.2~20.2ns
R12C R12C E220 0.90
R12C E220 R12C
E220 D219
E189 E220 K222 E220 R12C
K222
4. 12 R12C 10 10.2~20.2ns
R12C 10 10.2~20.2ns
R12C 1 R12C 1 1.46
R12C T219 R12C
E220 E189
2 D219 R218 T219
R12C 1 E220 R12C
D219 E189 E220
R222 E220 E189 R12C R222
4. 13 R12C 11 10.2~20.2ns
4. 14 R12C 11 10.2~20.2ns
4.1.1.2 GFOGER E11C E11D
(1) GFOGER E11C
C Glu OE1
Mg2+ C Glu Mg2+
E11C Mg2+
4. 15 C Glu OE1 Mg2+
10.2~20.2ns
4. 16 C Glu OE1 Mg2+
10.2~20.2ns
C Glu OE1 Mg2+
( 4. 15 C Glu OE1
Mg2+ ( 4. 15 Glu OE1
Mg2+
4. 17 C Glu OE1 Mg2+
(2) GFOGER E11D
D Glu
0
E11D (
0 Arg E11D T219 E11D
4. 18 E11D 1 2 0 1 10.2~20.2ns
4. 1 E11D 0 1 10.2~20.2ns
4. 19 E11D 0 1
10.2~20.2ns
4. 20 E11D 0 1 10.2~20.2ns
R12B R12C E11D
(3.1 (1.4 (2.0
(1.5
0 (1.4
R12B R12C E11D 1 11
10
4. 21 R12B R12C E11D
10.2~20.2ns [31]
4.1.2 GFOGER
GFOGER Phe CZ
Mg2+ F
D Phe B Phe
C Phe B Phe MIDAS C Phe
MIDAS B
Phe C Phe
4. 22 Phe
4. 23 B C D GFOGER Phe CZ
Mg2+ 10.2~20.2ns
B Phe
B Phe 4. 22 (2.7
(2.1 (1.9 4. 22
F8B Y157
2 0 1 F8B
Y285 L286 0.7 Y286( L286
L287 0.8 Y285( L286 1.5
1 Y284( L286 0.1
4. 24 F8B
10.2~20.2ns
B Phe Y157
L286 2.5 Y285 F8B
0.2 F8B
Y156 Y285 2.5 0
F8B 0 Y157 L287 1.7
Y286 F8B 0.1
1 F8B Y157 2.0 Y284
F8B 0.1
0
Y286 Y285
4. 25 F8B 10.2~20.2ns( :
Y157
4.1.3 GFOGER PI-stacking
B Phe PI-stacking
B Phe PI-stacking 4. 24
4. 24 PI-
stacking F8B Y157 PI-stacking
2 PI-stacking 0 1 PI-stacking F8B
Y285 PI-stacking 0.2 Y286 Y284( Y285(
Y286( PI-stacking 1.5 PI-stacking 1 0.1
PI-stacking
4. 26 F8B PI-stacking
10.2~20.2ns
PI-stacking B Phe Y157
2.0 PI-stacking F8B Y156 Y285
2.5 PI-stacking 0 0
F8B 0 Y157 1.0 PI-stacking 1 1
F8B Y157 2.0 PI-stacking
PI-stacking (conserved
PI-stacking PI-stacking
Y157 PI-stacking Y156 Y285
PI-stacking Y286
Y285 Y157 PI-stacking
4. 27 F8B PI-stacking 10.2~20.2ns( :
Y157 PI-stacking
4.1.4 GFOGER
GFOGER
R12B
R12C E11D 1 2 11
10
PI-stacking B Phe
PI-stacking 10
GFOGER
1.R12B R12C E11D
2.F8B
3.F8B PI-stacking
4. 28 R12B R12C E11D 1
10.2~20.2ns [31]
4. 29 F8B 10.2~20.2ns [31]
4. 30 F8B PI-stacking
10.2~20.2ns [31]
4.2 GLOGER
4.2.1 GLOGER
4.2.1.1 GLOGER R12B
B Arg
B Arg
S257 0.7 E255
E298 1.8
1 S258 E292 0.6 GFOGER
GLOGER R12B Glu Ser
4. 2 GLOGER R12B
10.2~20.2ns
4. 3 GFOGER R12B
10.2~20.2ns
E255 E298 R12B
S257 1 S258 E292
GLOGER B Arg
Glu Ser
4. 31 R12C
10.2~20.2ns
4.2.1.2 GLOGER R12C E11D
C Arg
R12C D219
GFOGER R12C T219 E220
GFOGER E220 R12C
GFOGER R12C E220
GFOGER 1 R12C Q219 GFOGER
R218 Q219 D
Glu E11D R218 1.6 0
R219 1.2 T219 0.5 (
0 Arg GLOGER E11D GFOGER
4. 4 GLOGER R12C E11D
10.2~20.2ns
4. 5 GFOGER R12C E11D
10.2~20.2ns
GLOGER R12C E11D GFOGER
R12C H258 D219 2.74 H258 R12C
R12C D219 R12C
D219
4. 32 R12C 10.2~20.2ns
R12C 10.2~20.2ns
R12C Q219 0.76 R12C Q219
E11D R218 1.64 E11D R218
GFOGER R218 GLOGER E11D
Phe Leu R218 E11D
4. 33 R12C 1 10.2~20.2ns
R12C 1 10.2~20.2ns
R12C H258 E220 1.42 H258 R12C
R12C E220 D219
E11D R219 1.64 E11D
R219 GFOGER 0 R219
GLOGER E11D Phe Leu R219
E11D
4. 34 R12C 10 10.2~20.2ns
R12C 10 10.2~20.2ns
GLOGER R12C E11D GFOGER
R12C T219 E220 2.44 2
D219 R218 T219 R12C R12C
T219 R12C E220
D219 E220 E11D
T219 0.46 E11D T219
4. 35 R12C 11 10.2~20.2ns
R12C 11 10.2~20.2ns
GLOGER R12B R12C E11D 0 GLOGER
1 4. 34
GLOGER R12B
R12C E11D 0
4. 36 GLOGER R12B R12C E11D
10.2~20.2ns [39]
4. 37 GFOGER (
[31]
4.2.2 GLOGER
B Leu 0
Y157
1.8 1.0 0.3
286 L286( Y285(
0.3 Y286( 1.4
157 286
4. 6 L8B 0 10.2~20.2ns
4. 7 F8B 10.2~20.2ns
B Leu Y157
L286 2.1 GFOGER
L F Leu Y156
Y285 0.6 GFOGER
L F S284 N286
0 Leu Y157 Y286 2.4
GFOGER L287 Y157 Y286
1 F8B Y157
0.9 GFOGER
4. 38 L8B 10.2~20.2ns( :
Y157
4.2.3 GLOGER
GLOGER
R12B R12C E11D
B Phe
GFOGER GLOGER
GLOGER 2 10
11 4. 37 4. 38
4. 39 GFOGER
10.2~20.2ns [39]
4. 40 GLOGER
10.2~20.2ns [39]
4.3 GAOGER
4.3.1 GAOGER
GFOGER GLOGER GAOGER R12B R12C E11D
B Arg GFOGER E256 S257
0.3 GLOGER 0.7 GAOGER 0.2
C Arg GFOGER H258 D219 2.9 GLOGER
2.7 GAOGER 2.6 D Glu
4. 41 R12B R12C E11D 10.2~20.2ns
4. 8 R12B R12C E11D 10.2~20.2ns
4.3.2 GAOGER A8
BPI-stacking
GFOGER GLOGER GAOGER 8B
Y157 Y285 L286 GAOGER Y157
0.3 GFOGER 1.9 GLOGER 1.8
Ala
GFOGER GLOGER GAOGER 8B
PI-stacking Leu Ala PI-stacking GFOGER
PI-stacking 2.2 Y157 Y285
4. 42 GFOGER GLOGER GAOGER
10.2~20.2ns
4. 43 GFOGER GLOGER GAOGER PI-stacking
10.2~20.2ns( : Y157 PI-stacking
4. 44 A8B 10.2~20.2ns
4.3.3 GAOGER
GFOGER GLOGER GAOGER
R12B R12C E11D
2
PI-stacking B Phe
GLOGER 2 GAOGER 2
4. 45 R12B R12C E11D 10.2~20.2ns
[30]
4. 46 GFOGER GLOGER GAOGER PI-
stacking 10.2~20.2ns
5.1 GFOGER
5. 1 Backbone of I-GFOGER complex
5.1.1 GFOGER
B Cit C
Cit D Glu
GFOGER GFOGER
GFOGER
5. 1 R12B R12C E11D
10.2~20.2ns
CIR12-Side GLU255-Side 0.06 CIR12-Side SER257-Main 0.02
CIR12-Side ASP292-Side 0.16 CIR12-Side GLU292-Side 0.02
0.02 0.06 0.16 0.02
HSE258-Side CIR12-Main 0.30
CIR12-Main ASP219-Main 0.82 CIR12-Main ARG218-Main 0.02 CIR12-Main THR219-Main 0.22 ARG219-Side CIR12-Side 0.02
CIR12-Side GLN219-Side 0.02 THR221-Main CIR12-Side 0.22
1.12 0.04 0.02 0.44
0.00 ARG218-Side GLU11-Side 1.56 ARG219-Side GLU11-Side 0.34 THR219-Side GLU11-Side 0.10 CitA11-D CitA10-D
CitA2-D CitA1-D
CitA1-B
CitA2-C CitA1-C
CitA10-B CitA11-B
SUM SUM SUM SUM
CitA2-B
CitA10-C CitA11-C
SUM SUM SUM SUM
ARG12-Side THR221-Side 0.02 ARG12-Side GLU256-Side 0.02 ARG12-Side GLU255-Side 0.54
ARG12-Side SER257-Main 0.24
ARG12-Side HSE257-Side 0.18 ARG12-Side HSE258-Side 0.16 ARG12-Side ASP257-Main 0.28
0.26 0.72 0.16 0.30
HSE258-Side ARG12-Main 0.72
ARG12-Main ASP219-Main 0.86 ARG12-Main ARG218-Main 0.48 ARG12-Main ARG219-Main 0.02 ARG12-Main THR219-Main 0.44 ARG12-Side ASP219-Side 1.28
ARG12-Side GLN219-Side 0.02 ARG12-Side GLU220-Side 0.90 ARG12-Side GLU220-Side 0.74 ARG12-Side GLU189-Side 0.28
2.86 0.50 0.92 1.46
0.00 ARG218-Side GLU11-Side 0.32 ARG219-Side GLU11-Side 0.32 THR219-Side GLU11-Side 0.24
SUM SUM SUM SUM
A2-D A1-D A10-D A11-D
A2-C A1-C A10-C A11-C
A2-B A1-B A10-B A11-B
SUM SUM SUM SUM
5. 2 R12B R12C E11D
10.2~20.2ns
C Cit H258 D219 1.1 GFOGER
1.7 Cit12C D219
Cit12C H258 D219
Cit12C Cit12C
GFOGER 2
( 3.1 1.1
5. 3 R12C Cit12C
10.2~20.2ns 2 1 10 11
GFOGER Cit12C D219 N189
L220 N222 N190 N189
L220 Cit12C Cit12C
N222 N190
L220 N189 N190 N222
5. 4 R12C Cit12C
10.2~20.2ns
C Cit R218 GFOGER Cit12C
0.5 D Glu R218 1.6
GFOGER 1.2 Cit12C R218
R218 E11D
GFOGER ( 1.5
1.7
5. 5 R12C Cit12C
10.2~20.2ns
GFOGER Q219 Cit12C
E188 R218
Cit12C E188 N189
M221 E11D
R218 Q219 Cit12C
5. 6 R12C 1 Cit12C 1
10.2~20.2ns
5. 7 Cit12C E11D [5]
C Cit E220 GFOGER Cit12C
0.9 D Glu R219(
0.3 GFOGER ( 0.3
E11D R219 Cit12C 0
GFOGER 0 (
1.4 0.5
5. 8 R12C Cit12C
10.2~20.2ns
GFOGER E220 Cit12C
K222 N222
M221 K222
E220 Cit12C
E220 S190 K222
5. 9 R12C Cit12C
10.2~20.2ns
5. 10 Cit12C E11D 10 [5]
C Cit 11 E220 E189 T221
GFOGER Cit12C 0.8 Cit12C
T219 GFOGER 0.2
D Glu T219 GFOGER 0.1
Cit12C E11D T219
GFOGER 1 (1.4 0.5
5. 11 R12C Cit12C
10.2~20.2ns
GFOGER E189 E220 R222
R222 K222 Cit12C
5. 12 R12C Cit12C
10.2~20.2ns
5. 13 Cit12C E11D 11 [5]
Cit12C
( D219 E188 E189
E220
N222 M221
K222 R222
5. 13 3.1 1.1
1.5 1.7 1.4
0.5 2.0 0.6
Cit12B Cit12C E11D
5. 14 GFOGER GFOGER
( [5]
5. 15 Cit12B Cit12C
E11D
10.2~20.2ns
5.1.2 GFOGER
GFOGER B Phe
F8B
5. 15 0.2 0.3
0.9
5. 16 GFOGER
10.2~20.2ns
5. 2 GFOGER
10.2~20.2ns
TYR157-Side PHE8-Side 1.94 TYR156-Side PHE8-Side 1.08 TYR157-Side PHE8-Side 1.01 TYR157-Side PHE8-Side 2.00 TYR285-Side PHE8-Side 0.23
LEU286-Side PHE8-Side 0.48 TYR285-Side PHE8-Side 1.42 TYR286-Side PHE8-Side 0.12 TYR284-Side PHE8-Side 0.09 LEU287-Side PHE8-Side 0.72
2.65 2.50 1.85 2.09
A2-B A1-B A10-B A11-B
SUM SUM SUM SUM
TYR157-Side PHE8-Side 2.02 TYR156-Side PHE8-Side 0.51 TYR157-Side PHE8-Side 0.79 TYR157-Side PHE8-Side 1.75 TYR285-Side PHE8-Side 0.04
LEU286-Side PHE8-Side 0.38 TYR285-Side PHE8-Side 1.71 TYR286-Side PHE8-Side 0.21
2.44 SUM 2.22 1.00 1.75
SUM SUM SUM
CitA1-B CitA10-B CitA11-B
CitA2-B
2 Y157 L286
F8B L287 F8B Y157
Y286
B Phe
GFOGER
5. 17 GFOGER F8B
10.2~20.2ns( : Y157
5.1.3 GFOGER PI-stacking
GFOGER B Phe PI-
stacking F8B PI-stacking
5. 17 0.1
0.3 PI-stacking
5. 18 GFOGER PI-stacking
10.2~20.2ns
5. 3 GFOGER PI-stacking
10.2~20.2ns
TYR157-Side PHE8-Side 1.94 TYR156-Side PHE8-Side 1.08 TYR157-Side PHE8-Side 1.01 TYR157-Side PHE8-Side 2.00 TYR285-Side PHE8-Side 0.23
TYR285-Side PHE8-Side 1.42 TYR286-Side PHE8-Side 0.12 TYR284-Side PHE8-Side 0.09
2.17 2.50 1.13 2.09
A2-B A1-B A10-B
SUM SUM SUM SUM
A11-B
TYR157-Side PHE8-Side 2.02 TYR156-Side PHE8-Side 0.51 TYR157-Side PHE8-Side 0.79 TYR157-Side PHE8-Side 1.75 TYR285-Side PHE8-Side 0.04
TYR285-Side PHE8-Side 1.71 TYR286-Side PHE8-Side 0.21
2.06 2.22 1.00 1.75
CitA2-B CitA1-B CitA10-B CitA11-B
SUM SUM SUM SUM
5. 19 GFOGER F8B
PI-stacking 10.2~20.2ns( : Y157 PI-stacking
5.1.4 GFOGER
GFOGER
Cit12B Cit12C
E11D
PI-stacking
B Phe
5. 20 Cit12B Cit12C E11D
10.2~20.2ns
5. 21 GFOGER
10.2~20.2ns
5. 22 GFOGER PI-
stacking 10.2~20.2ns
5. 23 GFOGER (
[5]
5.2 GLOGER
5.2.1 GLOGER
GLOGER Cit12B Cit12C E11D
0 GLOGER
3.4 3.2
2.2 0 1.1
B Cit 2.4 ( 3.2
0.7 ( 2.2 1 0.6 ( 3.4
B Cit
Cit E298
E255
C Cit 2.8 1.5
1.1 0.8
5. 24 Cit12B Cit12C E11D
10.2~20.2ns
5. 4 Cit12B Cit12C E11D
10.2~20.2ns
ARG12-Side GLU256-Main 0.02 ARG12-Side GLU255-Side 0.58 ARG12-Side SER258-Side 0.22
ARG12-Side SER257-Main 0.68 ARG12-Side GLU298-Side 1.82 ARG12-Side GLU292-Side 0.36
0.70 2.40 0.00 0.58
HSE258-Side ARG12-Main 0.54 HSE258-Side ARG12-Main 0.16
ARG12-Main ASP219-Main 0.90 ARG12-Main THR219-Main 0.64
ARG12-Side ASP219-Side 1.30
ARG12-Main GLN219-Side 0.76 ARG12-Side GLU220-Side 1.26 ARG12-Side GLU220-Side 1.80
2.74 0.76 1.42 2.44
0.00 ARG218-Side GLU11-Side 1.64 ARG219-Side GLU11-Side 1.22 THR219-Side GLU11-Side 0.46
A2-B A1-B A10-B A11-B
SUM SUM SUM SUM
A2-C A1-C A10-C A11-C
SUM SUM SUM SUM
A2-D A1-D A10-D A11-D
ARG287-Side CIR12-Side 0.02 CIR12-Side HSE256-Side 0.02
SER291-Side CIR12-Side 0.04
0.00 0.06 0.00 0.02
HSE258-Side CIR12-Main 0.50 CIR12-Side ASP258-Side 0.22 CIR12-Side SER258-Side 0.02
CIR12-Main ASP219-Main 0.78
1.28 0.22 0.00 0.02
0.00 ARG218-Side GLU11-Side 1.34 ARG219-Side GLU11-Side 1.58 0.00
CitA2-C CitA1-C CitA10-C CitA11-C
SUM SUM SUM SUM
CitA2-D CitA1-D CitA10-D
CitA2-B CitA1-B CitA10-B CitA11-B
SUM SUM SUM SUM
CitA11-D
C Cit H258 D219 1.3 GLOGER
1.6 Cit12C D219
Cit12C H258 D219
Cit12C Cit12C
( 1.1 (Cit12C
1.5
5. 25 R12C Cit12C
10.2~20.2ns
Cit12C D219 Cit12C
Cit12C H258 D219 ( 1.1
5. 26 R12C Cit12C 10.2~20.2ns
C Cit Q219 Cit12C
D258 ( 0.2 GLOGER
0.5 D Glu R218 1.3 GLOGER
0.3 Cit12C
D259 E11D R218
(Cit12C 0.8
5. 27 R12C Cit12C
10.2~20.2ns
GLOGER E11D R218 ( 1.3
Cit12C D258 ( 0.2
5. 28 R12C Cit12C 10.2~20.2ns
C Cit E220 H258 GLOGER
Cit12C 1.4 D Glu 0 R219(
1.6 GLOGER 0.4
Cit12C 0 E220 E11D
R219 (Cit12C
1.1
5. 29 R12C Cit12C
10.2~20.2ns
GLOGER E11D R219 Cit12C
E220
5. 30 R12C Cit12C 10.2~20.2ns
C Cit E220 T221 GLOGER
Cit12C 2.9 D Glu T219
GLOGER 0.5 Cit12C
1 Cit12C E220
E11D T221 (Cit12C
2.8
5. 31 R12C Cit12C
10.2~20.2ns
5. 32 R12C Cit12C 10.2~20.2ns
5.2.2 GLOGER
GLOGER L8B
Leu
0.3 0.4
0 0.4 0.7
157 286
157
0.2 0.4 0 0.2 0.3
286 0.1 0
0.2 0.5
5. 33 GLOGER
10.2~20.2ns
5. 5 GLOGER
10.2~20.2ns
0 0.4 0.7
Leu Y156 Y285
5. 34 GLOGER L8B
10.2~20.2ns( : Y157
5.2.3 GLOGER
C Cit
Cit12C Cit12C
E220 E11D
0 E220
R219 E11D
R218 E11D Cit12C
B Cit
0
5. 35 Cit12B Cit12C E11D
10.2~20.2ns GLOGER
10.2~20.2ns
5.3 GAOGER
5.3.1 GAOGER
GFOGER GLOGER GAOGER
GAOGER 2.6 GLOGER
2.2 GFOGER 2.0 GFOGER GLOGER
Cit12B GAOGER Cit12B
Cit12C Cit12C 1.4
GER Cit12B Cit12C
5. 36 GFOGER GLOGER GAOGER Cit12B Cit12C
E11D 10.2~20.2ns
5. 6 GFOGER GLOGER GAOGER Cit12B Cit12C
E11D 10.2~20.2ns
CIR12-Side SER257-Main 0.02 CIR12-Side SER257-Main 0.16
CIR12-Side HSE258-Main 0.02
0.02 0.00 0.18
HSE258-Side CIR12-Main 0.30 HSE258-Side CIR12-Main 0.50 HSE258-Side CIR12-Main 0.06 CIR12-Main ASP219-Main 0.82 CIR12-Main ASP219-Main 0.78 CIR12-Main ASP219-Main 0.72
1.12 1.28 0.78
SUM
CitL-C CitA-C
SUM SUM
CitA-B
SUM CitF-C
CitF-B CitL-B
SUM SUM
ARG12-Side GLU256-Side 0.02 ARG12-Side GLU256-Main 0.02 ARG12-Side GLU256-Main 0.06 ARG12-Side SER257-Main 0.24 ARG12-Side SER257-Main 0.68 ARG12-Side SER257-Main 0.16
0.26 0.70 0.22
HSE258-Side ARG12-Main 0.72 HSE258-Side ARG12-Main 0.54 HSE258-Side ARG12-Main 0.68 ARG12-Main ASP219-Main 0.86 ARG12-Main ASP219-Main 0.90 ARG12-Main ASP219-Main 0.54 ARG12-Side ASP219-Side 1.28 ARG12-Side ASP219-Side 1.30 ARG12-Side ASP219-Side 1.32
2.86 2.74 2.54
SUM SUM
F-B L-B A-B
F-C L-C
SUM
SUM SUM SUM
A-C
5.3.2 GAOGER PI-stacking
GFOGER GLOGER GAOGER
GFOGER 0.2
GLOGER 0.2 GAOGER 0.1
Y157 GFOGER GLOGER
2.0 GAOGER 0.9 Y285
GFOGER GLOGER L286 0.4
GFOGER GLOGER GAOGER B
8 PI-stacking
GFOGER PI-stacking 0.1
GFOGER F8B
PI-stacking
5. 37 GFOGER GLOGER GAOGER
10.2~20.2ns
5. 38 GFOGER PI-stacking
10.2~20.2ns
5. 39 GAOGER A8B 10.2~20.2ns
5.3.3 GFOGER GLOGER GAOGER
5. 39 GAOGER 5. 42 GAOGER
GAOGER 2.6
5. 40 GFOGER GLOGER GAOGER Cit12B
Cit12C E11D 10.2~20.2ns
5. 41 GFOGER GLOGER GAOGER
10.2~20.2ns
5. 42 GFOGER PI-stacking
10.2~20.2ns
5. 43
GAOGER
[3]
6.1
6.1.1 GFOGER
GFOGER R12B R12C E11D
F8B PI-stacking
(Y286 Y285
