Biomedical Engineering Reference
In-Depth Information
LIE
Linear interaction energy
LQTS
The long QT syndrome
MD
Molecular dynamics
MEP
Molecular electrostatic potential
MM-PBSA
Molecular mechanics - Poisson Boltzmann/surface area
MP2
The second order Møller-Plesset perturbation theory
MTX
Maurotoxin
nAChR
Nicotinic acetylcholine receptor
NCIDS
National cancer institute diversity set
NMR
Nuclear magnetic resonance
PAAs
Phenylalkylamines
PB
Phasic block
PcTx1
Psalmotoxin 1
POPC
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
QC
Quantum chemical calculations
QM/MM
Quantum mechanics/molecular mechanics
QSAR
Quantitative structure-activity relationships
RMSF
Root-mean-square fluctuations
RyR
Ryanodine receptor
TI
Thermodynamic integration
TTX
Tetrodotoxin
VGSCs
Voltage-gated sodium channels
Vpu
Viral protein U
1 Significance and Background
1.1
Ion Channels as Targets for Drugs
Ion channels are a subtype of integral transmembrane proteins (IDP). The determi-
nation of potassium channel structure by MacKinnon R. and co-workers [
1
] was the
first to reveal that ions passing through the ion channel can induce different
molecular signals. As these discoveries have had a significant impact on the
scientific community, Peter Agre [
2
], for his earlier work on the related IDP,
aquaporin, and Roderick MacKinnon were awarded the Nobel Prize in Chemistry
in 2003.
Ion channels are found in every living cell. The channels are complex integral
transmembrane proteins and function as a pathway for ion flow in and out of cells.
These mechanisms lead to neurotransmission or signaling processes that can trigger
or inhibit downstream physiological cell actions. Therefore, ion channels are
associated with several diseases such as Alzheimer's disease, schizophrenia, epi-
lepsy, anxiety disorders [
3
,
4
], Parkinson's disease [
5
], cancer [
6
,
7
], Lambert-Eaton
myasthenic syndrome [
8
], and cardiovascular disease [
9
-
11
].
