Gupta S.P. (ed.) Ion Channels and Their Inhibitors
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Membrane proteins (cont.)
functional discrimination
channels and pores, 25
characteristic features, amino acid
residues, 21–23
databases, 18–21
ion channel proteins, 26
transporters, different classes and
families, 23–25
transporters from globular proteins, 21
structural discrimination
b-barrel membrane proteins, 9–13
spanning b-strand segments, 13–17
TMH proteins, 4–8
TMS proteins, 8–9
TMH and TMS proteins, 2
transporters, 3
Membrane spanning b-strand segments
machine-learning techniques, 16–17
statistical methods, 14–15
Mexiletine, 67
Migraine, 86, 88, 91, 96, 98
Molecular dynamics (MD), 57–65, 70, 71
Molecular mechanics–Poisson Boltzmann/
surface area (MM-PBSA), 60, 61, 65
Molecular orbital partial atomic charge
(MOPAC), 244
Moricizine, 99
MS. See Multiple sclerosis
MTX. See Mallotoxin; Maurotoxin
Multiple sclerosis (MS), 90, 101, 254
Muscimol, 60
Myorelaxant, 246, 249, 252, 253
Myotonic syndromes, 86, 88–89, 98–99
N
Na
v
1.4, 67
Nervous system, 34, 35, 39, 46
N-methyl-
D-aspartate (NMDA) receptor, 60
N,N-diisopropyl amide, 135
Notch, 128
O
Other Cl
–
transporting systems
apolar cells, 328, 329
blockers of, 328
furosemide, 328
Na
2+
/2Cl
–
/K
+
carrier, 328
piretanide, 328
torasemide, 329
triflocine, 329
Outward rectifying chloride channels (ORCC),
316
Oxacarbazepine, 97
P
Pacemaker heart, 39, 40
Pain, 86–88, 91, 94–98, 101, 103
inflammatory, 87, 94–95
neuropathic, 87, 94–98
Pancreas, 243, 247–248, 252, 253
Parkinson, 55
Parkinson disease (PD), 90, 101
Partial least square (PLS), 244, 247, 251
Patch clamp, 57, 59
PcTx1. See Psalmotoxin 1
PD. See Parkinson disease
Pentameric proteins, 317, 318
Pharmacophore, 67
Phenytoin, 92–96, 98, 99, 103
Plasma membrane, 311, 312, 316, 317, 330,
331
Plateau, 128, 132
Pore-forming region (P-region), 119
“Positive-inside rule” concept, 6
Potassium channel, 117–142
Potassium channel openers (KCOs), 61
Prialt, 290, 292, 294, 295
Principle components regression (PCR), 244
Protein Data Bank (PDB), 3–4
Psalmotoxin 1 (PcTx1), 58, 59
Q
QM/MM. See Quantum mechanics/molecular
mechanics
QSAR. See Quantitative structure activity
relationships
QT interval correction (QTc), 159–160
QT-prolonging, 65–67
Quantitative structure activity relationships
(QSAR), 65–68, 71, 273, 274,
276–278, 281, 282
Quantum mechanics/molecular mechanics
(QM/MM), 70–71
Quinidine, 120, 140
Quinoline, 129–130
R
Ralfinamide, 97
Ranolazine, 99–100
Recognition, 59, 64
346 Index
Remacemide, 101
retro-QSAR, 261
Root-mean-square fluctuations (RMSF), 62
RSD1235, 101
Ryanodine receptor (RyR), 69
S
Safinamide, 101
SAN. See Sinoatrial node
SAR. See Structure activity relationships
Schizophrenia, 55
Scoring function, 58, 63, 65
Sertindole, 58, 63
SHAKE, 65
Shaker, 60
Sinoatrial node (SAN), 34, 37, 39, 40, 42, 44
Sinus rhythm (SR), 138–139
Spermine, 59
STERIMOL parameters, 255
Structural discrimination, membrane proteins
b-barrel membrane proteins, 9–13
spanning b-strand segments, 13–17
TMH proteins, 4–8
TMS proteins, 8–9
Structure activity relationships (SAR),
272–278
Structure-based approaches
amino acids involvement, 220–222
binding affinity model, 225–226
binding interactions, 225
docking results, 229–232
docking studies, 227–228
drug trapping, 218–220
Gly648 role, 223
homology models, 217–218
hydrogen bonds with Thr623, Ser624 and
Val625, 222–223
orthogonal binding site, 229
para-substituents influence on phenyl ring,
224–225
subunits involvement, 223–224
Subunits, 83, 85–91
a, 82–88, 98, 119
b, 82–83, 86, 87, 89, 101, 119
T
Tdp. See Torsades de pointes
Tedisamil, 139–140
Tetrahydroindolone, 125–126
Tetrahydronaphthyls, 126–127, 130
Tetrazole, 123–125
Tetrodotoxin (TTX), 70, 85, 95, 101, 103
Thalamic rhythm, 39
Thermodynamics, 57, 61, 63, 66–68
1,2,4-Thiadiazines, 61
Thiazolidinone, 123–125
Thyrotoxicosis, 45
Tocainide, 67
Topiramate, 94, 96, 98, 101, 102
TOPP, 61
Torsades de pointes (Tdp), 120, 132, 139
description, 158–159
drug-induced QT prolongation, 160–163
Transmembrane domains, 316
Transmembrane helical (TMH) proteins
features, 4
spanning region prediction
HMM, 6–7
machine-learning methods, 7
multiple sequence alignment, 7
statistical methods, 5–6
Web servers, 8
Transmembrane strand (TMS) proteins
rules, 8–9
Web servers, 12
Transporter Classification Database (TCDB),
18–19
Transporters, membrane proteins
based on different classes and families,
23–25
from globular proteins, 21
Triarylethanolamine, 136
Tripos force field, 61
TTX. See Tetrodotoxin
V
Validation, 62–63
Ventricular effective refractory period
(VERP), 122, 124, 126, 129
Vernakalant, 101, 138
VERP. See Ventricular effective refractory
period
VGSCs. See Voltage-gated sodium channels
VolSurf procedure, 61
Voltage dependent Ca
2+
, 266
Voltage-gated channels, 243
Voltage-gated potassium channel (Kv), 56
Kv1, 63
Kv1.3, 57, 60, 63
Kv1.5, 59, 63, 64
KvAP channel, 62
Voltage-gated sodium channels (VGSCs), 67
Voltage sensing domains (VSDs), 155
Index 347
W
Wannier functions, 70
Weighted holistic invariant molecular (WHIM)
descriptors, 254
X
Xenopus oocytes, 249
Y
Yanoguanidines, 61
Z
Zatebradine, 41–43
ZD 7288, 41, 45–46
Zonisamide, 94, 102
348 Index