Biomedical Engineering Reference
In-Depth Information
Table 1 Published homology models of the hERG potassium channel in the closed and open state
References Template
Homology model/docking
[
6
]
KcsA (1BL8)
Insight II/FLOG
[
5
]
KcsA (1BL8)
MOE/FLOG
[
21
]
MthK (1LNQ)
Modeller
[
4
]
KcsA (1BL8)
QUANTA/CHARMm/Manual docking
[
119
]
KcsA (1BL8)
SWISS-MODEL/Chimera
[
12
]
KcsA (1BL8)
Modeller v6.0/GOLD
[
11
]
KcsA (1BL8), MthK (1LNQ)
Insight II/FlexiDock
[
89
]
KcsA (1K4C), MthK (1LNQ)
PRIME/Glide
[
105
]
KcsA (1BL8)
Modeller v6.0/GOLD
[
98
]
KvaP (1ORQ)
SWISS-MODEL/AutoDock 3.0
[
88
]
KcsA (1BL8), MthK (1LNQ)
Insight II/FlexiDock
[
97
]
KvaP (1R3J)
Modeller v.8.0/GOLD v.2.2
[
49
]
MthK (1LNQ)
MOE/Glide
[
99
]
KvaP (1ORQ)
PRIME/Glide 3.0
[
120
]
Kv1.2 (2A79)
SWISS-MODEL/AutoDock 3.0
[
90
]
KcsA (1BL8)
SWISS-MODEL/ZDOCK
[
95
]
KvaP (1ORQ)
Modeller v6.0/Sievgene
[
96
]
KvaP (1ORQ)
Modeller
[
100
]
KcsA (1BL8), Kv1.2 (2A79)
QUANTA/Manual docking
[
39
]
KcsA (1BL8)
Insight II/DOCK v.5.2
[
121
]
KcsA (1BL8)
Moloc/Manual docking
[
91
]
KcsA (1K4C), KvaP (1ORQ)
Modeller v.7.7/GOLD v.3.0.1
[
92
]
KcsA (1BL8)
Modeller v.7.7/Insight II/GOLD v.3.1
[
116
]
KcsA (1BL8)
Insight II/Manual docking
[
93
]
KcsA (1BL8)
Modeler v6.0/GOLD
MthK (1LNQ), KvaP (1ORQ), KcsA
(1BL8)
Modeler v.6.2 and Modeler v.7.7/
GOLD v.3.0
[
94
]
[
117
]
MthK (1LNQ)
Modeler v.8.2
[
38
]
Kcsa (1R3J)
Insight II/Glide
[
104
]
KcsA (1BL8)
Insight II/FLOG
[
102
]
KcsA (1K4C)
Modeller/FlexX
[
118
]
KcsA (2BOB, 2HjF and 2HVK)
Modeller/GOLD
in the open state were constructed with the crystal structures of KvaP (1ORQ, or
1R3J) [
91
,
94
-
99
] and Kv1.2 (2A79) [
100
] used as template (Table
1
).
5.2 hERG Inhibition and Drug Trapping
In 1969, Armstrong [
101
] demonstrated that the channel opening is a necessary
condition to obtain the inhibition of the voltage gated K
+
channel by a small
quaternary ammonium (QA) ion. Normally, the QA interferes with the channel
gating upon repolarization causing a slow deactivation due to the impossibility to
close the activation gate in a mechanism called “foot-in-the-door.” In a few words,
