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Review
. 2012 Dec 12;112(12):6250-84.
doi: 10.1021/cr3002609. Epub 2012 Oct 4.

Modeling and simulation of ion channels

Christopher Maffeo  1 , Swati Bhattacharya, Jejoong Yoo, David Wells, Aleksei Aksimentiev
Affiliations
Review

Modeling and simulation of ion channels

Christopher Maffeo et al. Chem Rev. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Evolution of the equivalent circuit diagrams of nerve axon models. (a) Schematic representation of an axon. Conductance experiments are performed by maintaining a given transmembrane voltage and measuring the resulting ionic current. (b) Cable model of the axon. (c) Refined model including a (variable) membrane emf and variable membrane resistance. (d) Hodgkin- Huxley model, which describes the emfs and conductivities of potassium and sodium separately, and also includes a small leakage current.
Figure 2
Figure 2
Conductance of squid axon membrane to sodium (a) and potassium (b) at various applied voltages. Voltage was held at the rest value of −65 mV, then increased to the displayed value at t = 0. While potassium conductance rises and saturates under an applied potential, sodium conductance initially rises but subsequently returns to zero. Adapted with permission from Reference 397. Copyright 1952 Wiley.
Figure 3
Figure 3
(a, b) Schematics of potassium (a) and sodium (b) channels considered in the Hodgkin- Huxley model. In the HH model, the conductance of a potassium channel is controlled by four activating particles (black circles), while the conductance of a sodium channel is controlled by three activating particles and one inactivating particle (gray circle). (c, d) Behavior of the HH model variables describing potassium (c) and sodium (d) conductance as a function of applied potential.
Figure 4
Figure 4
Molecular graphics images of membrane channels listed in Table 1. The channels shown are: (a) gramicidin A (gA), 1JNO; (b) mechanosensitive channel of large conductance (MscL), 2OAR; (c) mechanosensitive channel of small conductance (MscS), 2OAU; (d) ammonium transporter (AmtB), 2NUU; (e) K+ channel (KcsA), 3EFF; (f) voltage-gated K+ channel (Kv), 2R9R; (g) aquaporin 0 (AQP0), 2B6O; (h) nicotinic acetylcholine receptors (nAchR), 2BG9;, (i) bacterial outer-membrane porin (OmpF), 2OMF; (j) bacterial chloride channel (ClC), 1OTS; (k) bacterial toxin (α-hemolysin), 7AHL.
Figure 5
Figure 5
Pore region of the KcsA K+ ion channel embedded in a lipid bilayer membrane. The image shows the first crystallographically determined structure of a K+ channel, which did not include the long cytoplasmic helices depicted in Figure 4e. One of the four subunits of the KcsA tetramer is not shown to provide a clear view of the selectivity filter. The lipid bilayer is depicted as grey van der Waals spheres.
Figure 6
Figure 6
Comparison of the pores formed by seven TM3 helices of MscS in nonconducting (a) and open (b) conformations, viewed from the periplasm (top) and from within the membrane (bottom).
Figure 7
Figure 7
A schematic illustrations of the PNP (a) BD (b) and all-atom MD (c) modeling methods applied to the same system—an α-hemolysin channel embedded in a lipid bilayer membrane and surrounded by an electrolyte solution. In panel (a), the ions are described as continuous density, whereas the water, protein and membrane are treated as continuum dielectric media. In the BD model (panel b), only ions are represented explicitly, whereas all other components are either implicitly modeled or approximated by continuum media. All atoms are treated explicitly in the all-atom MD method (panel c).
Figure 8
Figure 8
Thermodynamic cycle for calculations of a pKa shift. RH and R− denote protonated and deprotonated states, respectively, of a titratable group. The gray box indicates a region near a protein or a membrane. ΔGref and ΔG denote free energies of deprotonation in water and in protein or membrane environment, respectively. ΔG1 and ΔG2 are transfer free energies of RH and R− from water to protein or membrane environment, respectively.
Figure 9
Figure 9
The selectivity filter of KcsA. The system is depicted as in Figure 5, but additionally with K+ ions resolved in the X-ray structure (orange spheres). In the active state, the selectivity filter will always contain at least two K+ ions separated by a single water molecule.
Figure 10
Figure 10
Na+ (green sphere) and K+ (red spheres) ions occupy different binding sites in the selectivity filter of a potassium channel. Early FEP simulations indicated a large free energy cost ΔΔG for exchanging K+ with Na+ at the K+binding sites. ΔΔG may actually be smaller if the ion is free to move to its preferred binding site. Adapted with permission from Macmillan Publishers Ltd: Nature Structural & Molecular Biology (Reference 595), copyright 2009.
Figure 11
Figure 11
(a) Cut-away view of the full-length MspA nanopore embedded in a lipid membrane with a DNA strand threaded through. The MspA is represented by a teal molecular surface, the lipid membrane by purple lines and the DNA bases are shown in magenta colored licorice representation. (b) Average electrostatic potentials along the symmetry axis of the full and truncated MspA nanopores at a transmembrane bias of 180 mV. The electrostatic potentials are computed from MD simulations of open pore MspA nanopores. (c) Cut-away view of the reduced MspA system. The DNA is covalently joined to itself across the periodic boundary. (d) The ionic current trace of a sample trajectory in of a poly(dC) strand threaded through the MspA nanopore. (e) Ionic current histograms obtained from ensemble simulations of the M1 MspA (yellow) and its arginine variant, M1 L88R/A96R/S116R (blue). The overlap of the two histograms is shown in green. The histograms were constructed using 100 ns averages of the instantaneous ionic current. Adapted with permission from Reference 348. Copyright 2012. American Chemical Society.
See this image and copyright information in PMC

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