Molecular dynamics simulations of voltage-gated cation channels: Insights on voltage-sensor domain function and modulation

Frontiers in Pharmacology

Volumn 3 MAY, Issue , 2012, Pages

  Delemotte, Lucie ^a,b   Klein, Michael L ^b   Tarek, Mounir ^a  

^a UNIVERSITÉ DE LORRAINE   (France)

^b Temple University   (United States)

Author keywords

Channelopathies; Gating charges; Kv1.2; Molecular models; Mutations; Omega currents; VSD intermediate states

Indexed keywords

CATION CHANNEL; UNCLASSIFIED DRUG; VOLTAGE GATED CATION CHANNEL;

ANALYTIC METHOD; ARTICLE; BINDING SITE; BIOSENSOR; CHANNEL GATING; CHANNELOPATHY; CRYSTAL STRUCTURE; CRYSTALLIZATION; ELECTRIC FIELD; ELECTROPHYSIOLOGY; HYDROPHILICITY; HYDROPHOBICITY; HYPERPOLARIZATION; ION PERMEABILITY; LIPID BILAYER; MATHEMATICAL ANALYSIS; MEMBRANE DEPOLARIZATION; MOLECULAR DYNAMICS; PROTEIN CONFORMATION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; PROTEIN STABILITY; PROTEIN STRUCTURE; SIMULATION; STRUCTURAL HOMOLOGY; UBIQUITINATION; VALIDITY;

EID: 84866023433     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2012.00097     Document Type: Article

References (145)

1. Aggarwal, S. K., and MacKinnon, R. (1996). Contribution of the S4 segment to gating charge in the Shaker K+ channel. Neuron 16, 1169-1177.
2. Aksimentiev, A., and Schulten, K. (2005). Imaging a-hemolysin with molecular dynamics: ionic conductance, osmotic permeability, and the electrostatic potential map. Biophys. J. 88, 3745-3761.
3. Allen, M. P., and Tildesley, D. J. (1987). Computer Simulation of Liquids. Oxford: Clarendon Press.
4. Armstrong, C. M., and Bezanilla, F. (1973). Currents related to movement of the gating particles of the sodium channels. Nature 242, 459-461.
5. Asamoah, O. K., Wuskell, J. P., Loew, L. M., and Bezanilla, F. (2003). A fluorometric approach to local electric field measurements in a voltagegated ion channel. Neuron 37,85-97.
6. Baker, O., Larsson, H., Mannuzzu, L., and Isacoff, E. (1998). Three transmembrane conformations and sequence-dependent displacement of the S4 domain in Shaker K channel gating. Neuron 20, 1283-1294.
7. Bao, H., Hakeem, A., Henteleff, M., Starkus, J. G., and Rayner, M. D. (1999). Voltage-insensitive gating after charge-neutralizing mutations in the S4 segment of Shaker channels. J. Gen. Physiol. 113, 139-151.
8. Beckstein, O., Biggin, P. C., Bond, P., Bright, J. N., Domene, C., Grottesi, A., Holyoake, J., and Sansom, M. S. P. (2003). Ion channel gating: insights via molecular dynamics. FEBS Lett. 555, 85-90.
9. Bezanilla, F. (2005). The voltage-sensor structure in a voltage-gated ion channel. Trends Biochem. Sci. 30, 166-168.
10. Bjelkmar, P., Niemelä, P. S., Vattulainen, I., and Lindahl, E. (2009). Conformational changes and slow dynamics through microsecond polarized atomistic molecular simulation of an integral Kv1.2 ion channel. PLoS Comput. Biol. 5, e1000289. doi:10.1371/journal.pcbi.1000289
11. Bond, P. J., Holyoake, J., Ivetac, A., Khalid,S.,and Sansom,M. S. (2007). Coarse-grained molecular dynamics simulations of membrane proteins and peptides. J. Struct. Biol. 157, 593-605.
12. Bond, P. J., and Sansom, M. S. P. (2007). Bilayer deformation by the Kv channel voltage sensor domain revealed by self-assembly simulations. Proc. Natl. Acad. Sci. U.S.A. 104, 2631-2636.
13. Börjesson, S. I., and Elinder, F. (2008). Structure, function, and modification of the voltage sensor in voltagegated ion channels. Cell Biochem. Biophys. 52, 149-174.
14. Bostick,D.,and Berkowitz,M. L. (2003). The implementation of slab geometry for membrane-channel molecular dynamics simulations. Biophys. J. 85, 97-107.
15. Broomand, A., Männikkö, R., Larsson, P., and Elinder, F. (2003). Molecular movement of the voltage sensor in a K channel. J. Gen. Physiol. 122, 741-748.
16. Capener, C. E., and Sansom, M. S. P. (2002). Molecular dynamics simulations of a K+ channel model: sensitivity to changes in ions, waters, and membrane environment. J. Phys. Chem. 106, 4543-4551.
17. Carnevale, V., Treptow, W., and Klein, M. L. (2011). Sodium ion binding sites and hydration in the lumen of a bacterial ion channel from molecular dynamics simulations. J. Phys. Chem. Lett. 2, 2504-2508.
18. Case, D. A., Pearlman, D. A., Caldwell, J. W., Cheatham, III T. E., Ross, W. S., Simmerling, C. L., Darden, T. A., Merz, K. M., Stanton, R. V., and Cheng, A. L. (1999). AMBER6.San Francisco: University of California.
19. Catterall, W. A. (2010). Ion channel voltage sensors: structure, function, and pathophysiology. Neuron 67, 915-928.
20. Chen, X., Wang, Q., Ni, F., and Ma, J. (2010). Structure of the full-length Shaker potassium channel Kv1. 2 by normal-mode-based X-ray crystallographic refinement. Proc. Natl. Acad. Sci. U.S.A. 107, 11352.
21. Clayton, G., Altieri, S., Heginbotham, L., Unger, V., and Morais-Cabral, J. (2008). Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel. Proc. Natl. Acad. Sci. U.S.A. 105, 1511-1515.
22. Corry, B., and Thomas, M. (2011). Mechanism of ion permeation and selectivity in a voltage gated sodium channel. J. Am. Chem. Soc. 134, 1840-1846.
23. Crozier, P. S., Henderson, D., Rowley, R. L., and Busath, D. D. (2001). Model channel ion currents in NaCl extended simple point charge water solution with applied-field molecualr dynamics. Biophys. J. 81, 3077-3089.
24. DeCaen, P. G., Yarov-Yarovoy, V., Scheuer, T., and Catterall, W. A. (2011). Gating charge interactions with the S1 segment during activation of a Na+ channel voltage sensor. Proc. Natl. Acad. Sci. U.S.A. 108, 18825-18830.
25. DeCaen, P. G., Yarov-Yarovoy, V., Sharp, E. M., Scheuer, T., and Catterall, W. A. (2009). Sequential formation of ion pairs during activation of a sodium channel voltage sensor. Proc. Natl. Acad. Sci. U.S.A. 106, 22498.
26. del Camino, D., Holmgren, M., Liu, Y., and Yellen, G. (2000). Blocker protection in the pore of a voltagegated K+ channel and its structural implications. Nature 403, 321-325.
27. Delemotte, L., Dehez, F., Treptow, W., and Tarek, M. (2008). Modeling membranes under a transmembrane potential. J. Phys. Chem. B 112, 5547-5550.
28. Delemotte, L., and Tarek, M. (2012). Molecular dynamics simulations of lipid membranes electroporation. J. Memb. Biol. doi:10.1007/s00232-012-9434-6
29. Delemotte, L., Tarek, M., Klein, M. L., Amaral, C., and Treptow, W. (2011). Intermediate states of the Kv1.2 voltage sensor from atomistic molecular dynamics simulations. Proc. Natl. Acad. Sci. U.S.A. 108, 6109-6114.
30. Delemotte, L., Treptow, W., Klein, M. L., and Tarek, M. (2010). Effect of sensor domain mutations on the properties of voltage-gated ion channels: molecular dynamics studies of the potassium channel Kv1.2. Biophys. J. 99, L72-L74.
31. Denning, E. J., Crozier, P. S., Sachs, J. N., and Woolf, T. B. (2009). From the gating charge response to pore domain movement: initial motions of Kv1.2 dynamics under physiological voltage changes. Mol. Membr. Biol. 26, 397-421.
32. Devane, R., Shinoda, W., Moore, P. B., and Klein, M. L. (2009). A transferable coarse grain nonbonded interaction model for amino acids. J. Chem. Theory. Comput. 5, 2115-2124.
33. Domene, C., Haider, S., and Sansom, M. S. P. (2003). Ion channel structures: a review of recent progress. Curr. Opin. Drug Discov. Devel. 6, 611-619.
34. Doyle, D. A., Cabral, J. M., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T., and MacKinnon, R. (1998). The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69-77.
35. Durell, S. R., Shrivastava, I. H., and Guy, H. R. (2004). Models of the structure and voltage-gating mechanism of the Shaker K+ channel. Biophys. J. 87, 2116-2130.
36. Eriksson, M. A. L., and Roux, B. (2002). Modeling the structure of Agitoxin in complex with the Shaker K+ channel: a computational approach based on experimental distance restraints extracted from thermodynamic mutant cycles. Biophys. J. 83, 2595-2609.
37. Freites, J. A., Tobias, D. J., and White, S. H. (2006). A voltage-sensor water pore. Biophys. J. 91, L90-L92.
38. Frenkel, D., and Smit, B. (2002). Molecular Simulations-From Algorithms to Applications, 2nd Edn. Salt Lake City: Academic Press.
39. Gamal El-Din, T. M., Heldstab, H., Lehmann, C., and Greeff, N. G. (2010). Double gaps along Shaker S4 demonstrate omega currents at three different closed states. Channels (Austin) 4, 93-100.
40. Grabe, M., Lai, H. C., Jain, M., Jan,Y. N., and Jan, L. Y. (2007). Structure prediction for the down state of a potassium channel voltage sensor. Nature 445, 550-553.
41. Grabe, M., Lecar, H., Jan, Y. N., and Jan, L. Y. (2004). A quantitative assessment of models for voltage-dependent gating ion channels. Proc. Natl. Acad. Sci. U.S.A. 101, 17640-17645.
42. Gumbart, J., Khalili-Araghi, F., Sotomayor, M., and Roux, B. (2012). Constant electric field simulations of the membrane potential illustrated with simple systems. Biochim. Biophys. Acta 1818, 294-302.
43. Gurtovenko, A. A., and Vattulainen, I. (2005). Pore formation coupled to ion transport through lipid membranes as induced by transmembrane ionic charge imbalance: atomistic molecular dynamics study. J. Am. Chem. Soc. 127, 17570-17571.
44. Guy, H. R. (2002). Computational simulations of peptide binding to proteins: how scorpions sting K+ channels. Biophys. J. 83, 2325-2326.
45. Han, M., and Zhang, J. Z. H. (2008). Molecular dynamic simulation of the Kv1.2 voltage-gated potassium channel in open and closed state conformations. J. Phys. Chem. B 112, 6966-16974.
46. Hénin, J., and Chipot, C. (2004). Overcoming free energy barriers using unconstrained molecular dynamics simulations. J. Chem. Phys. 121, 2904-2914.
47. Hille, B. (2001). Ion Channels of Excitable Membranes, 3rd Edn. Sunderland: Sinauer Associates.
48. Islas, L. D., and Sigworth, F. J. (2001). Electrostatic and the gating pore of Shaker potassium channels. J. Gen. Physiol. 117, 69-89.
49. Jensen, M. Ø., Borhani, D. W., Lindorff-Larsen, K., Maragakis, P., Jogini, V., Eastwood, M. P., Dror, R. O., and Shaw, D. E. (2010). Principles of conduction and hydrophobic gating in K+ channels. Proc. Natl. Acad. Sci. U.S.A. 107, 5833-5838.
50. Jensen, M. Ø., Jogini, V., Borhani, D. W., Leffler, A. E., Dror, R. O., and Shaw, D. E. (2012). Mechanism of voltage gating in potassium channels. Science 336, 229-233.
51. Jiang, Y., Lee, A., Chen, J., Ruta, V., Cadene, M., Chait, B. T., and MacKinnon, R. (2003a). X-ray structure of a voltage-dependent K+ channel. Nature 423, 33-41.
52. Jiang, Y., Ruta, V., Chen, J., Lee, A., and MacKinnon, R. (2003b). The principle of gating charge movement in a voltage-dependent K+ channel. Nature 423, 42-48.
53. Jogini, V., and Roux, B. (2007). Dynamics of the Kv1. 2 voltage-gated K+ channel in a membrane environment. Biophys. J. 93, 3070-3082.
54. Jurkat-Rott, K., Mitrovic, N., Hang, C., Kouzmekine, A., Iaizzo, P., Herzog, J., Lerche, H., Nicole, S., Vale-Santos, J., Chauveau, D., Fontaine, B., and Lehmann-Horn, F. (2000). Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Proc. Natl. Acad. Sci. U.S.A. 97, 9549-9554.
55. Kandasamy, S. K., and Larson, R. G. (2006). Cation and anion transport through hydrophilic pores in lipid bilayers. J. Chem. Phys. 125, 074901.
56. Kanevsky,M.,andAldrich,R.W. (1999). Determinants of voltage-dependent gating and open-state stability in the S5 segment of Shaker potassium channels. J. Gen. Physiol. 114, 215-242.
57. Keynes, R. D., and Rojas, E. (1974). Kinetics and steady-state properties of the charged system controlling sodium conductance in the squid giant axon. J. Gen. Physiol. 239, 393-434.
58. Khalfa, A., Treptow, W., Maigret, B., and Tarek, M. (2009). Self assembly of peptides near or within membranes using coarse grained MD simulations. Chem. Phys. 358, 161-170.
59. Khalili-Araghi, F., Jogini, V., YarovYarovoy, V., Tajkhorshid, E., Roux, B., and Schulten, K. (2010). Calculation of the gating charge for the Kv1.2 voltage-activated potassium channel. Biophys. J. 98, 2189-2198.
60. Khalili-Araghi,F.,Tajkhorshid,E.,Roux, B., and Schulten, K. (2012). Molecular dynamics investigation of the ωcurrent in the Kv1.2 voltage sensor domains. Biophys. J. 102, 258-267.
61. Klassen, T. L., Spencer,A. N., and Gallin, W. J. (2008). A naturally occurring omega current in a Kv3 family potasium channel from a platyhelminth. BMC Neurosci. 9, 52-64. doi:10.1186/1471-2202-9-52
62. Krepkiy, D., Mihailescu, M., Freites, J. A., Schow, E. V., Worcester, D. L., Gawrisch, K., Tobias, D. J., White, S. H., and Swartz, K. J. (2009). Structure and hydration of membranes embedded with voltage-sensing domains. Nature 462, 473-479.
63. Kutzner, C., Grubmüller, H., de Groot, B. L., and Zachariae, U. (2011). Computational electrophysiology: the molecular dynamics of ion channel permeation and selectivity in atomistic detail. Biophys. J. 101, 809-817.
64. Laio, A., and Gervasio, F. L. (2008). Metadynamics: a method to simulate rare events and reconstruct the free energy in biophysics, chemistry and material science. Rep. Prog. Phys. 71, 126601.
65. Leach, A. R. (2001). Molecular Modeling-Principles and Applications, 2nd Edn. Upper Saddle River: Pearson Education Limited.
66. Lecar, H., Larsson, H. P., and Grabe, M. (2003). Electrostatic model of S4 motion in voltage-gated ion channels. Biophys. J. 85, 2854-2864.
67. Lehmann-Horn, F., and Jurkat-Rott, K. (1999). Voltage-gated ion channels and hereditary disease. Physiol. Rev. 79, 1517.
68. Lin, M. A., Hsieh, J.-Y., Mock, A. F., and Papazian, D. M. (2011). R1 in the Shaker S4 occupies the gating charge transfer center in the resting state. J. Gen. Physiol. 138, 155-163.
69. Loboda, A., and Armstrong, C. M. (2001). Resolving the gating charge movement associated with late transitions in K channel activation. Biophys. J. 81, 905-916.
70. Long, B. S., Campbell, E. B., and Mackinnon, R. (2005a). Voltage sensor of Kv1.2: Structural basis of electromechanical coupling. Science 309, 903-908.
71. Long, B. S., Campbell, E. B., and MacKinnon, R. (2005b). Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309, 897-903.
72. Long, S. B., Tao, X., Campbell, E. B., and MacKinnon, R. (2007). Atomic structure of a voltage-dependent K+channel in a lipid membrane-like environment. Nature 450, 376-382.
73. MacKerell, J. A. D., Bashford, D., Bellott, M., Dunbrack, R. L., Evanseck, J. D., Field, M. J., Fischer, S., Gao, J., Guo, H., Ha, S., Joseph McCarthy, D., Kuchnir, L., Kuczera, K., Lau, F. T. K., Mattos, C., Michnick, S., Ngo, T., Nguyen, D. T., Prodhom, B., Reiher, W. E., Roux, B., Schlenkrich, M., Smith, J. C., Stote, R., Straub, J., Watanabe, M., Wiorkiewicz-Kuczera, J., Yin, D., and Karplus, M. (1998). Allatom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 102, 3586-3616.
74. Maragliano, L., Fischer, A., VandenEijnden, E., and Ciccotti, G. (2006). String method in collective variables: minimum free energy paths and isocommittor surfaces. J. Chem. Phys. 125, 024106-24115.
75. Marrink, S. J., Risselda, H. J., Yelfinov, S., Tieleman, D. P., and De Vries, A. H. (2007). The MARTINI force field: coarse grained model for biomolecular simulations. J. Phys. Chem. B 111, 7812-7824.
76. Martyna, G. J., Tuckerman, M. E., and Klein, M. L. (1992). Nosé-hoover chains: the canonical ensemble via continuous dynamics. J. Chem. Phys. 97, 2635-2643.
77. Matthes, D., and De Groot, B. L. (2009). Secondary structure propensities in peptide folding simulations: a systematic comparison of molecular mechanics interaction schemes. Biophys. J. 97, 599-608.
78. Miceli, F., Soldovieri, M. V., Hernandez, C. C., Shapiro, M. S., Annunziato, L., and Taglialatela, M. (2008). Gating consequences of charge neutralization of arginine residues in the S4 segment of Kv7.2, an epilepsy-linked K+ channel subunit. Biophys. J. 95, 2254-2264.
79. Mokrab, Y., and Sansom, M. S. P. (2011). Interaction of diverse voltage sensor homologs with lipid bilayers revealed by self-assembly simulations. Biophys. J. 100, 875-884.
80. Neale, E. J. (2003). Evidence for intersubunit interactions between S4 and S5 transmembrane segments of the Shaker potassium channel. J. Biol. Chem. 278, 29079-29085.
81. Nishizawa, M., and Nishizawa, K. (2008). Molecular dynamics simulation of Kv channel voltage sensor helix in a lipid membrane with applied electric field. Biophys. J. 95, 1729-1744.
82. Nishizawa, M., and Nishizawa, K. (2009). Coupling of S4 helix translocation and S6 gating analyzed by molecular-dynamics simulations of mutated Kv channels. Biophys. J. 97, 90-100.
83. Noda, M., Shimizu, S., Tanabe, T., Takai, T., Kayano, T., Ikeda, T., Takahashi, H., Nakayama, H., Kanaoka, Y., and Minamino, N. (1984). Primary structure of electrophorus electricus sodium channel deduced from cDNA sequence. Nature 312, 121-127.
84. Nonner, W., Peyser, A., Gillespie, D., and Eisenberg, B. (2004). Relating microscopic charge movement to macroscopic currents: the Ramo-Schockley theorem applied to ion channels. Biophys. J. 87, 3716-3722.
85. Papazian, D. M., Shao, X. M., Seoh, S., Mock, A. F., Huang, Y., and Wainstock, D. H. (1995). Electrostatis interactions of S4 voltage sensor in Shaker K+ channel. Neuron 14, 1293-1301.
86. Pathak, M. M., Yarov-Yarovoy, V., Agarwal, G., Roux, B., Barth, P., Kohout, S., Tombola, F., and Isaccoff, E. Y. (2007). Closing in on the resting state of the Shaker K+ channel. Neuron 56, 124-140.
87. Payandeh, J., Scheuer, T., Zheng, N., and Catterall, W. A. (2011). The crystal structure of a voltage-gated sodium channel. Nature 475, 353-358.
88. Perozo, E., MacKinnon, R., Bezanilla, F., and Stefani, E. (1993). Gating currents from a nonconducting mutant reveal open-closed conformations in Shaker K+ channels. Neuron 11, 353-358.
89. Ramu, Y., Xu, Y., and Lu, Z. (2006). Enzymatic activation of voltagegated potassium channels. Nature 442, 696-699.
90. Ranatunga, K. M., Law, R. J., Smith, G. R., and Sansom, M. S. (2001). Eletrostatics studies and molecular dynamics simulations of a homology model of the Shaker K+ channel pore. Eur. Biophys. J. 30, 295-303.
91. Roux, B. (2008). The membrane potential and its representation by a constant electric field in computer simulations. Biophys. J. 95, 4205-4216.
92. Roux, B. T. (1997). Influence of the membrane potential on the free energy of an intrinsic protein. Biophys. J. 73, 2980-2989.
93. Ruta, V., Chen, J., and Mackinnon, R. (2005). Calibrated measurement of gating-charge arginine displacement in the KvAP voltage-dependent K+ channel. Cell 123, 463-475.
94. Sachs, J. N., Crozier, P. S., and Woolf, T. B. (2004). Atomistic simulations of biologically realistic transmembrane potential gradients. J. Chem. Phys. 121, 10847-10851.
95. Sands, Z. A., and Sansom, M. S. P. (2007). How does a voltage sensor interact with a lipid bilayer? Simulations of a potassium channel domain. Structure 15, 235-244.
96. Schmidt, D., Jiang, Q., and MacKinnon, R. (2006). Phospholipids and the origin of cationic gating charges in voltage sensors. Nature 444, 775-779.
97. Schneider, M. F., and Chandler, W. K. (1973). Voltage dependent charge movement in skeletal muscle: a possible step in excitationcontraction coupling. Nature 242, 244-246.
98. Schoppa, N. E., McCormack, K., Tanouye, M. A., and sigworth, F. J. (1992). The size of gating charge in wild-type and mutant Shaker potassium channels. Science 255, 1712-1715.
99. Schoppa, N. E., and Sigworth, F. J. (1998). Activation of Shaker potassium channels. III. An activation gating model for wild-type and V2 mutant channel. J. Gen. Physiol. 111, 313-342.
100. Schow, E. V., Freites, J. A., Gogna, K., White, S. H., and Tobias, D. J. (2010). Down-state model of the voltage-sensing domain of a potassium channel. Biophys. J. 98, 2857-2866.
101. Schuler, L. D., Daura, X., and van Gunsteren, W. F. (2001). An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase. J. Comput. Chem. 22, 1205-1218.
102. Schwaiger, C. S., Bjelkmar, P., Hess, B., and Lindahl, E. (2011). 310helix conformation facilitates the transition of a voltage sensor S4 segment toward the down state. Biophys. J. 100, 1446-1454.
103. Selvin, P. R. (2002). Principles and biophysical applications of lanthanidebased probes. Annu. Rev. Biophys. Biomol. Struct. 31, 275-302.
104. Seoh,S.A.,Sigg,D.,Papazian,D. M.,and Bezanilla, F. (1996). Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel. Neuron 16, 1159-1167.
105. Shafrir, Y., Durell, S. R., and Guy, H. R. (2008). Models of voltagedependent conformational changes in NaChBac channels. Biophys. J. 95, 3663-3676.
106. Shaw,D., Dror, R.,Salmon, J.,Grossman, J., Mackenzie, K., Bank, J., Young, C., Deneroff, M., Batson, B., Bowers, K., Chow, E., Eastwood, M. P., Ierardi, D. J., Klepeis, J. L., Kuskin, J. S., Larson, R. H., Larsen, K. L., Maragakis, P., Moraes, M.A., Piana, S., Shan, Y.,and Towles, B. (2009)."Millisecond-scale molecular dynamics simulations on Anton," in SC '09: Proceedings of the Conference on High Performance Computing Networking, Storage and Analysis (Portland, OR: ACM), 1-11.
107. Sigg, D., Bezanilla, F., and Stefani, E. (2003). Fast gating in the Shaker K+ channel and the energy landscape of activation. Proc. Natl. Acad. Sci. U.S.A. 100, 7611-7615.
108. Sigworth, F. J. (1994). Voltage gating of ion channels. Q. Rev. Biophys. 27, 1-40.
109. Sokolov,S.,Scheuer,T.,and Catterall,W. A. (2005). Ion permeation through a voltage-sensitive gating pore in brain sodium channels having voltage sensor mutations. Neuron 47, 183-189.
110. Sokolov,S.,Scheuer,T.,and Catterall,W. A. (2007). Gating pore current in an inherited ion channelopathy. Nature 446, 76-78.
111. Sokolov, S., Scheuer, T., and Catterall, W. A. (2008). Depolarizationactivated gating pore current conducted by mutant sodium channels in potassium-sensitive normokalemic periodic paralysis. Proc. Natl. Acad. Sci. U.S.A. 105, 19980-19985.
112. Soldovieri, M. V., Miceli, F., Bellini, G., Coppola, G., Pascotto, A., and Tagliatela, M. (2007). Correlating the clinical and genetic features of benign familial neonatal seizures (BFNS) with the functional consequences of underlying mutations. Channels (Austin) 1, 228-233.
113. Starace, D. M., and Bezanilla, F. (2001). Histidine scanning mutagenesis of basic residues of the S4 segment of the Shaker potassium channel. J. Gen. Physiol. 117, 469-490.
114. Starace, D. M., and Bezanilla, F. (2004). A proton pore in a potassium channel voltage sensor reveals a focused electric field. Nature 427, 548-553.
115. Stefani, E., Toro, L., Perozo, E., and Bezanilla,F. (1994). Gating of Shaker K+ channels: I. Ionic and gating currents. Biophys. J. 66, 996-1010.
116. Struyk, A. F., and Cannon, S. C. (2007). ANa+ channel mutation linked to hypokalemic periodic paralysis exposes a proton selective gating Pore. J. Gen. Physiol. 130, 11-20.
117. Suenaga, A., Komeiji, Y., Uebayasi, M., Meguro, T., Saito, M., and Yamato, I. (1998). Computational observation of an ion permeation through a channel protein. Biosci. Rep. 18, 39-48.
118. Tao, X., Lee, A., Limapichat, W., Dougherty, D. A., and MacKinnon, R. (2010). A gating charge transfer center in voltage sensors. Science 328, 67-73.
119. Tarek, M. (2005). Membrane electroporation: a molecular dynamics simulation. Biophys. J. 88, 4045-4053.
120. Tempel, B. L., Papazian, D. M., Schwarz, T. L., Jan, Y. N., and Jan, L. Y. (1987). Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila. Science 237, 770-775.
121. Tieleman, D. P. (2004). The molecular basis of electroporation. BMC Biochem. 5, 10. doi:10.1186/1471-2091-5-10
122. Tieleman, D. P., Biggin, P. C., Smith, G. R.,and Sansom,M. S. P. (2001). Simulation approaches to ion channel structure-function relationships. Q. Rev. Biophys. 34, 473-561.
123. Tiwari-Woodruff, S. K., Lin, M. A., Schulteis, C. T., and Papazian, D. M. (2000).Voltage-dependent structural interactions in the Shaker K+ channel. J. Gen. Physiol. 115, 123-138.
124. Tombola, F., Pathak, M. M., Gorostiza, P., and Isacoff, E. Y. (2006a). The twisted ion-permeation pathway of a resting voltage-sensing domain. Nature 445, 546-549.
125. Tombola, F., Pathak, M. M., and Isacoff, E.Y. (2006b). How does voltage open an ion channel? Annu.Rev.Cell Dev. Biol. 22, 23-52.
126. Tombola, F., Pathak, M. M., and Isacoff, E. Y. (2005a). How far will you go to sense voltage? Neuron 48, 719-725.
127. Tombola, F., Pathak, M. M., and Isacoff, E. Y. (2005b). Voltagesensing arginines in a potassium channel permeate and occlude cation-selective pores. Neuron 45, 379-388.
128. Treptow,W., Maigret, B., Chipot, C., and Tarek, M. (2004). Coupled motions between pore and voltage-sensor domains: a model for Shaker B, a voltage-gated potassium channel. Biophys. J. 87, 2365-2379.
129. Treptow, W., Marrink, S. J., and Tarek, M. (2008). Gating motions in voltage-gated potassium channels revealed by coarse-grained molecular dynamics simulations. J. Phys. Chem. B 112, 3277-3282.
130. Treptow, W., and Tarek, M. (2006a). Environment of the gating charges in the Kv1.2 Shaker potassium channel. Biophys. J. 90, L64-L66.
131. Treptow, W., and Tarek, M. (2006b). K+ conduction in the selectivity filter of potassium channels is monitored by the charge distribution along their sequence. Biophys. J. 91, L81-L83.
132. Treptow, W., Tarek, M., and Klein, M. L. (2009). Initial response of the potassium channel voltage sensor to a transmembrane potential. J. Am. Chem. Soc. 131, 2107-2110.
133. Vargas, E., Bezanilla, F., and Roux, B. (2011). In search of a consensus model of the resting state of a voltage-sensing domain. Neuron 72, 713-720.
134. Wee, C. L., Gavaghan, D., and Sansom, M. S. P. (2008). Lipid bilayer deformation and the free energy of interaction of a Kv channel gating-modifier toxin. Biophys. J. 95, 3816-3826.
135. Wood, M. L., Schow, E. V., Freites, J. A., White, S. H., Tombola, F., and Tobias, D. J. (2012). Water wires in atomistic models of the Hv1 proton channel. Biochim. Biophys. Acta 1818, 286-293.
136. Wu, D., Delaloye, K., Zaydman, M. A., Nekouzadeh, A., Rudy, Y., and Cui, J. (2010). State-dependent electrostatic interactions of S4 arginines with E1 in S2 during Kv7.1 activation. J. Gen. Physiol. 135, 595-606.
137. Xu, Y., Ramu, Y., and Lu, Z. (2008). Removal of phospho-head groups of membrane lipids immobilizes voltage sensors of K+ channels. Nature 451, 826-829.
138. Yarov-Yarovoy, V., Baker, D., and Catterall, W. A. (2006). Voltage sensor conformations in the open and closed states in Rosetta structural models of K+ channels. Proc. Natl. Acad. Sci. U.S.A. 103, 7292-7297.
139. Yoda, T., Sugita, Y., and Okamoto, Y. (2004). Secondary-structure preferences of force fields for proteins evaluated by generalizedensemble simulations. Chem. Phys. 307, 269-283.
140. Zagotta,W. N.,Hoshi,T.,andAldrich,R. W. (1994a). Shaker potassium channel gating. III: Evaluation of kinetic models for activation. J. Gen. Physiol. 103, 321.
141. Zagotta, W. N., Hoshi, T., Dittman, J., and Aldrich, R. W. (1994b). Shaker potassium channel gating. II: Transitions in the activation pathway. J. Gen. Physiol. 103, 279-319.
142. Zhang, M., Liu, J., Jiang, M., Wu, D.-M., Sonawane, K., Guy, H. R., and Tseng, G.-N. (2005). Interactions between charged residues in the transmembrane segments of the voltage-sensing domain in the hERG channel. J. Membr. Biol. 207, 169-181.
143. Zheng, H., Liu, W., Anderson, L. Y., and Jiang, Q.-X. (2011). Lipid-dependent gating of a voltage-gated potassium channel. Nat. Commun. 2, 250.
144. Zheng, J., and Sigworth, F. J. (1998). Intermediate conductances during deactivation of heteromultimeric Shaker potassium channels. J. Gen. Physiol. 112, 457-474.
145. Zhong, Q., Jiang, Q., Moore, P. B., Newns, D. M., and Klein, M. L. (1998). Molecular dynamics simulation of a synthetic ion channel. Biophys. J. 74, 3-10.