Pathways and barriers for ion translocation through the 5-HT3A receptor channel

PLoS ONE

Volumn 10, Issue 10, 2015, Pages

  Di Maio, Danilo ^a   Chandramouli, Balasubramanian ^a   Brancato, Giuseppe ^a  

^a SCUOLA NORMALE SUPERIORE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

SEROTONIN 3A RECEPTOR; ION; SEROTONIN 3 RECEPTOR;

ALPHA HELIX; ARTICLE; CARBOXY TERMINAL SEQUENCE; CHANNEL GATING; CONTROLLED STUDY; CRYSTALLIZATION; HYDROPHOBICITY; ION CONDUCTANCE; ION TRANSPORT; LIPID BILAYER; MOLECULAR DYNAMICS; PROTEIN DOMAIN; PROTEIN FUNCTION; RECEPTOR BINDING; SOLVATION; STRUCTURE ANALYSIS; ANIMAL; CHEMISTRY; GENETICS; METABOLISM; MOLECULAR MODEL; MOUSE; MUTATION; PROTEIN CONFORMATION; SIGNAL TRANSDUCTION; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; IONS; MICE; MODELS, MOLECULAR; MUTATION; PROTEIN CONFORMATION; RECEPTORS, SEROTONIN, 5-HT3; SIGNAL TRANSDUCTION;

EID: 84949034076     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0140258     Document Type: Article

References (97)

1. Lemoine D, Jiang R, Taly A, Chataigneau T, Specht A, Grutter T (2012) Ligand-gated ion channels: new insights into neurological disorders and ligand recognition. Chemical reviews 112: 6285-6318. doi: 10.1021/cr3000829 PMID: 22988962
2. Nys M, Kesters D, Ulens C (2013) Structural insights into Cys-loop receptor function and ligand recognition. Biochemical Pharmacology 86: 1042-1053. doi: 10.1016/j.bcp.2013.07.001 PMID: 23850718
3. Thompson AJ, Lester HA, Lummis SCR (2010) The structural basis of function in Cys-loop receptors. Quarterly Reviews of Biophysics 43: 449-499. doi: 10.1017/S0033583510000168 PMID: 20849671
4. Dougherty DA (2008) Cys-Loop Neuroreceptors: Structure to the Rescue? Chemical Reviews 108: 1642-1653. doi: 10.1021/cr078207z PMID: 18447378
5. Bouzat C, Gumilar F, Spitzmaul G, Wang H-L, Rayes D, Hansen SB, et al. (2004) Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel. Nature 430: 896-900. PMID: 15318223
6. Imoto K, Busch C, Sakmann B, Mishina M, Konno T, Nakai J, et al. (1988) Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance. Nature 335: 645-648. PMID: 2459620
7. Lee WY, Sine SM (2005) Principal pathway coupling agonist binding to channel gating in nicotinic receptors. Nature 438: 243-247. PMID: 16281039
8. Lummis SCR, Beene DL, Lee LW, Lester HA, Broadhurst RW, Dougherty DA (2005) Cis-trans isomerization at a proline opens the pore of a neurotransmitter-gated ion channel. Nature 438: 248-252. PMID: 16281040
9. Beckstein O, Sansom MS (2006) A hydrophobic gate in an ion channel: the closed state of the nicotinic acetylcholine receptor. Phys Biol 3: 147-159. PMID: 16829701
10. Calimet N, Simoes M, Changeux JP, Karplus M, Taly A, Cecchini M (2013) PNAS Plus: From the Cover: A gating mechanism of pentameric ligand-gated ion channels. Proceedings of the National Academy of Sciences 110: E3987-E3996.
11. Cheng X, Lu B, Grant B, Law RJ, McCammon JA (2006) Channel Opening Motion of a7 Nicotinic Acetylcholine Receptor as Suggested by Normal Mode Analysis. Journal of Molecular Biology 355: 310-324. PMID: 16307758
12. Ivanov I, Cheng X, Sine SM, McCammon JA (2007) Barriers to Ion Translocation in Cationic and Anionic Receptors from the Cys-Loop Family. Journal of the American Chemical Society 129: 8217-8224. PMID: 17552523
13. Law RJ, Henchman RH, McCammon JA (2005) A gating mechanism proposed from a simulation of a human a7 nicotinic acetylcholine receptor. Proceedings of the National Academy of Sciences of the United States of America 102: 6813-6818. PMID: 15857954
14. Nury H, Poitevin F, Van Renterghem C, Changeux JP, Corringer PJ, Delarue M, et al. (2010) Onemicrosecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue. Proceedings of the National Academy of Sciences 107: 6275-6280.
15. Xu Y, Barrantes FJ, Luo X, Chen K, Shen J, Jiang H (2005) Conformational Dynamics of the Nicotinic Acetylcholine Receptor Channel: A 35-ns Molecular Dynamics Simulation Study. Journal of the American Chemical Society 127: 1291-1299. PMID: 15669869
16. Corringer P-J, Poitevin F, Prevost Marie S, Sauguet L, Delarue M, Changeux J-P (2012) Structure and Pharmacology of Pentameric Receptor Channels: From Bacteria to Brain. Structure 20: 941-956. doi: 10.1016/j.str.2012.05.003 PMID: 22681900
17. van Dijk WJ, Klaassen RV, Schuurmans M, van der Oost J, Smit AB, Sixma TK, et al. (2001) Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411: 269-276. PMID: 11357122
18. daCosta Corrie JB, Baenziger John E (2013) Gating of Pentameric Ligand-Gated Ion Channels: Structural Insights and Ambiguities. Structure 21: 1271-1283. doi: 10.1016/j.str.2013.06.019 PMID: 23931140
19. Lee WY, Free CR, Sine SM (2009) Binding to Gating Transduction in Nicotinic Receptors: Cys-Loop Energetically Couples to Pre-M1 and M2-M3 Regions. Journal of Neuroscience 29: 3189-3199. doi: 10.1523/JNEUROSCI.6185-08.2009 PMID: 19279256
20. Grosman C, Zhou M, Auerbach A (2000) Mapping the conformational wave of acetylcholine receptor channel gating. Nature 403: 773-776. PMID: 10693806
21. Cymes GD, Grosman C, Auerbach A (2002) Structure of the Transition State of Gating in the Acetylcholine Receptor Channel Pore: A F-Value Analysis. Biochemistry 41: 5548-5555. PMID: 11969415
22. Purohit P, Gupta S, Jadey S, Auerbach A (2013) Functional anatomy of an allosteric protein. Nature Communications 4.
23. Limapichat W, Lester HA, Dougherty DA (2010) Chemical Scale Studies of the Phe-Pro Conserved Motif in the Cys Loop of Cys Loop Receptors. Journal of Biological Chemistry 285: 8976-8984. doi:10. 1074/jbc.M109.060939 PMID: 20068044
24. Melis C, Bussi G, Lummis SCR, Molteni C (2009) Transcis Switching Mechanisms in Proline Analogues and Their Relevance for the Gating of the 5-HT3 Receptor. The Journal of Physical Chemistry B 113: 12148-12153. doi: 10.1021/jp9046962 PMID: 19663504
25. Paulsen IM, Martin IL, Dunn SMJ (2009) Isomerization of the proline in the M2-M3 linker is not required for activation of the human 5-HT3A receptor. Journal of Neurochemistry 110: 870-878. doi: 10.1111/j. 1471-4159.2009.06180.x PMID: 19457066
26. Cheng X, Ivanov I, Wang H, Sine SM, McCammon JA (2007) Nanosecond-Timescale Conformational Dynamics of the Human a7 Nicotinic Acetylcholine Receptor. Biophysical Journal 93: 2622-2634. PMID: 17573436
27. Keramidas A, Lynch JW (2013) An outline of desensitization in pentameric ligand-gated ion channel receptors. Cellular and Molecular Life Sciences 70: 1241-1253. doi: 10.1007/s00018-012-1133-z PMID: 22936353
28. Kash TL, Jenkins A, Kelley JC, Trudell JR, Harrison NL (2003) Coupling of agonist binding to channel gating in the GABAA receptor. Nature 421: 272-275. PMID: 12529644
29. Zhu F, Hummer G (2010) Pore opening and closing of a pentameric ligand-gated ion channel. Proceedings of the National Academy of Sciences of the United States of America 107: 19814-19819. doi:10. 1073/pnas.1009313107 PMID: 21041674
30. Galzi JL, Devillers-Thiéry A, Hussy N, Bertrand S, Changeux JP, Bertrand D (1992) Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic. Nature 359: 500-505. PMID: 1383829
31. Corringer P-J, Bertrand S, Galzi J-L, Devillers-Thiéry A, Changeux J-P, Bertrand D (1999) Mutational analysis of the charge selectivity filter of the a7 nicotinic acetylcholine receptor. Neuron 22: 831-843. PMID: 10230802
32. Keramidas A, Moorhouse AJ, Pierce KD, Schofield PR, Barry PH (2002) Cation-selective mutations in the M2 domain of the inhibitory glycine receptor channel reveal determinants of ion-charge selectivity. The Journal of General Physiology 119: 393-410. PMID: 11981020
33. Wotring VE, Miller TS, Weiss DS (2003) Mutations at the GABA receptor selectivity filter: a possible role for effective charges. The Journal of Physiology 548: 527-540. PMID: 12626678
34. Peters JA, Cooper MA, Carland JE, Livesey MR, Hales TG, Lambert JJ (2010) Novel structural determinants of single channel conductance and ion selectivity in 5-hydroxytryptamine type 3 and nicotinic acetylcholine receptors. The Journal of Physiology 588: 587-596. doi: 10.1113/jphysiol.2009.183137 PMID: 19933751
35. Hansen SB, Wang HL, Taylor P, Sine SM (2008) An Ion Selectivity Filter in the Extracellular Domain of Cys-loop Receptors Reveals Determinants for Ion Conductance. Journal of Biological Chemistry 283: 36066-36070. doi: 10.1074/jbc.C800194200 PMID: 18940802
36. Barnes NM, Hales TG, Lummis SC, Peters JA (2009) The 5-HT3 receptor - the relationship between structure and function. Neuropharmacology 56: 273-284. doi: 10.1016/j.neuropharm.2008.08.003 PMID: 18761359
37. Lummis SCR (2012) 5-HT3 Receptors. Journal of Biological Chemistry 287: 40239-40245. doi:10. 1074/jbc.R112.406496 PMID: 23038271
38. Walstab J, Rappold G, Niesler B (2010) 5-HT3 receptors: Role in disease and target of drugs. Pharmacology & Therapeutics 128: 146-169. doi: 10.1016/j.pharmthera.2010.07.001 PMID: 20621123
39. Beene DL, Brandt GS, Zhong W, Zacharias NM, Lester HA, Dougherty DA (2002) Cation-pi interactions in ligand recognition by serotonergic (5-HT3A) and nicotinic acetylcholine receptors: the anomalous binding properties of nicotine. Biochemistry 41: 10262-10269. PMID: 12162741
40. Price KL, Bower KS, Thompson AJ, Lester HA, Dougherty DA, Lummis SCR (2008) A Hydrogen Bond in Loop A Is Critical for the Binding and Function of the 5-HT3 Receptor. Biochemistry 47: 6370-6377. doi: 10.1021/bi800222n PMID: 18498149
41. Sullivan NL, Sullivan NL, Thompson AJ, Price KL, Lummis SCR (2006) Defining the roles of Asn-128, Glu-129 and Phe-130 in loop A of the 5-HT3 receptor. Molecular Membrane Biology 23: 442-451. PMID: 17060161
42. Beene DL, Price KL, Lester HA, Dougherty DA, Lummis SC (2004) Tyrosine residues that control binding and gating in the 5-hydroxytryptamine3 receptor revealed by unnatural amino acid mutagenesis. J Neurosci 24: 9097-9104. PMID: 15483128
43. Thompson AJ, Lochner M, Lummis SCR (2008) Loop B Is a Major Structural Component of the 5-HT3 Receptor. Biophysical Journal 95: 5728-5736. doi: 10.1529/biophysj.108.135624 PMID: 18931259
44. Thompson AJ, Price KL, Reeves DC, Chan SL, Chau PL, Lummis SCR (2005) Locating an Antagonist in the 5-HT3 Receptor Binding Site Using Modeling and Radioligand Binding. Journal of Biological Chemistry 280: 20476-20482. PMID: 15781467
45. Reeves DC, Sayed MFR, Chau P-L, Price KL, Lummis SCR (2003) Prediction of 5-HT3 Receptor Agonist-Binding Residues Using Homology Modeling. Biophysical journal 84: 2338-2344. PMID: 12668442
46. Thompson AJ, Padgett CL, Lummis SCR (2006) Mutagenesis and Molecular Modeling Reveal the Importance of the 5-HT3 Receptor F-loop. Journal of Biological Chemistry 281: 16576-16582. PMID: 16595668
47. Thompson AJ, Chau PL, Chan SL, Lummis SCR (2006) Unbinding Pathways of an Agonist and an Antagonist from the 5-HT3 Receptor. Biophysical Journal 90: 1979-1991. PMID: 16387779
48. Panicker S, Cruz H, Arrabit C, Slesinger PA (2002) Evidence for a centrally located gate in the pore of a serotonin-gated ion channel. The Journal of neuroscience 22: 1629-1639. PMID: 11880493
49. Carland JE, Cooper MA, Livesey MR, Hales TG, Peters JA, Lambert JJ (2013) Mutagenic Analysis of the Intracellular Portals of the Human 5-HT3A Receptor. Journal of Biological Chemistry 288: 31592-31601. doi: 10.1074/jbc.M113.503300 PMID: 24030822
50. Gunthorpe MJ (2001) Conversion of the Ion Selectivity of the 5-HT3A Receptor from Cationic to Anionic Reveals a Conserved Feature of the Ligand-gated Ion Channel Superfamily. Journal of Biological Chemistry 276: 10977-10983. PMID: 11439930
51. Thompson AJ, Lummis SCR (2003) A single ring of charged amino acids at one end of the pore can control ion selectivity in the 5-HT3 receptor. British Journal of Pharmacology 140: 359-365. PMID: 12970096
52. Kelley SP, Dunlop JI, Kirkness EF, Lambert JJ, Peters JA (2003) A cytoplasmic region determines single-channel conductance in 5-HT3 receptors. Nature 424: 321-324. PMID: 12867984
53. Hassaine G, Deluz C, Grasso L, Wyss R, Tol MB, Hovius R, et al. (2014) X-ray structure of the mouse serotonin 5-HT3 receptor. Nature 512: 276-281. doi: 10.1038/nature13552 PMID: 25119048
54. Unwin N (2005) Refined Structure of the Nicotinic Acetylcholine Receptor at 4Å Resolution. Journal of Molecular Biology 346: 967-989. PMID: 15701510
55. Althoff T, Hibbs RE, Banerjee S, Gouaux E (2014) X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors. Nature 512: 333-337. doi: 10.1038/nature13669 PMID: 25143115
56. Pan J, Chen Q, Willenbring D, Yoshida K, Tillman T, Kashlan OB, et al. (2012) Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine. Nature Communications 3.
57. Nury H, Van Renterghem C, Weng Y, Tran A, Baaden M, Dufresne V, et al. (2011) X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nature 469: 428-431. doi:10. 1038/nature09647 PMID: 21248852
58. Wang H-L, Cheng X, Taylor P, McCammon JA, Sine SM (2008) Control of Cation Permeation through the Nicotinic Receptor Channel. PLoS Computational Biology 4.
59. Wang H-L, Toghraee R, Papke D, Cheng X-L, McCammon JA, Ravaioli U, et al. (2009) Single-Channel Current Through Nicotinic Receptor Produced by Closure of Binding Site C-Loop. Biophysical Journal 96: 3582-3590. doi: 10.1016/j.bpj.2009.02.020 PMID: 19413963
60. Sauguet L, Poitevin F, Murail S, Van Renterghem C, Moraga-Cid G, Malherbe L, et al. (2013) Structural basis for ion permeation mechanism in pentameric ligand-gated ion channels. The EMBO journal 32: 728-741. doi: 10.1038/emboj.2013.17 PMID: 23403925
61. Hales TG, Dunlop JI, Deeb TZ, Carland JE, Kelley SP, Lambert JJ, et al. (2006) Common Determinants of Single Channel Conductance within the Large Cytoplasmic Loop of 5-Hydroxytryptamine Type 3 and 4beta2 Nicotinic Acetylcholine Receptors. Journal of Biological Chemistry 281: 8062-8071. PMID: 16407231
62. Bouzat C, Bartos M, Corradi J, Sine SM (2008) The Interface between Extracellular and Transmembrane Domains of Homomeric Cys-Loop Receptors Governs Open-Channel Lifetime and Rate of Desensitization. Journal of Neuroscience 28: 7808-7819. doi: 10.1523/JNEUROSCI.0448-08.2008 PMID: 18667613
63. Reeves DC (2005) A Role for the β1-β2 Loop in the Gating of 5-HT3 Receptors. Journal of Neuroscience 25: 9358-9366. PMID: 16221844
64. Cheng X, Wang H, Grant B, Sine SM, McCammon JA, 2006, Targeted Molecular Dynamics Study of C-Loop Closure and Channel Gating in Nicotinic Receptors, PLoS Computational Biology 2.
65. Gao F, Bren N, Burghardt TP, Hansen S, Henchman RH, Taylor P, et al. (2005) Agonist-mediated Conformational Changes in Acetylcholine-binding Protein Revealed by Simulation and Intrinsic Tryptophan Fluorescence. Journal of Biological Chemistry 280: 8443-8451. PMID: 15591050
66. Henchman RH, Wang H-L, Sine SM, Taylor P, Andrew McCammon J (2005) Ligand-Induced Conformational Change in the a7 Nicotinic Receptor Ligand Binding Domain. Biophysical Journal 88: 2564-2576. PMID: 15665135
67. Liu X, Xu Y, Li H, Wang X, Jiang H, Barrantes FJ (2008) Mechanics of channel gating of the nicotinic acetylcholine receptor. PLoS computational biology 4.
68. Yi M, Tjong H, Zhou H-X (2008) Spontaneous conformational change and toxin binding in a7 acetylcholine receptor: Insight into channel activation and inhibition. Proceedings of the National Academy of Sciences 105: 8280-8285.
69. Reeves DC (2001) Structural and Electrostatic Properties of the 5-HT3 Receptor Pore Revealed by Substituted Cysteine Accessibility Mutagenesis. Journal of Biological Chemistry 276: 42035-42042. PMID: 11557761
70. Livesey MR, Cooper MA, Lambert JJ, Peters JA (2011) Rings of Charge within the Extracellular Vestibule Influence Ion Permeation of the 5-HT3A Receptor. Journal of Biological Chemistry 286: 16008-16017. doi: 10.1074/jbc.M111.219618 PMID: 21454663
71. Jansen M, Bali M, Akabas MH (2008) Modular Design of Cys-loop Ligand-gated Ion Channels: Functional 5-HT3 and GABA 1 Receptors Lacking the Large Cytoplasmic M3M4 Loop. The Journal of General Physiology 131: 137-146. doi: 10.1085/jgp.200709896 PMID: 18227272
72. Livesey MR, Cooper MA, Deeb TZ, Carland JE, Kozuska J, Hales TG, et al. (2008) Structural Determinants of Ca2+ Permeability and Conduction in the Human 5-Hydroxytryptamine Type 3A Receptor. Journal of Biological Chemistry 283: 19301-19313. doi: 10.1074/jbc.M802406200 PMID: 18474595
73. Hibbs RE, Gouaux E (2011) Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474: 54-60. doi: 10.1038/nature10139 PMID: 21572436
74. Bernèche S, Roux B (2001) Energetics of ion conduction through the K+ channel. Nature 414: 73-77. PMID: 11689945
75. Hilf RJC, Dutzler R (2008) X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 452: 375-379. doi: 10.1038/nature06717 PMID: 18322461
76. Deeb TZ, Carland JE, Cooper MA, Livesey MR, Lambert JJ, Peters JA, et al. (2006) Dynamic Modification of a Mutant Cytoplasmic Cysteine Residue Modulates the Conductance of the Human 5-HT3A Receptor. Journal of Biological Chemistry 282: 6172-6182.
77. Kozuska JL, Paulsen IM, Belfield WJ, Martin IL, Cole DJ, Holt A, et al. (2014) Impact of intracellular domain flexibility upon properties of activated human 5-HT3 receptors: 5-HT3 receptor intracellular domain significance. British Journal of Pharmacology 171: 1617-1628. doi: 10.1111/bph.12536 PMID: 24283776
78. Ilegems E, Pick H, Deluz C, Kellenberger S, Vogel H (2005) Ligand Binding Transmits Conformational Changes across the Membrane-Spanning Region to the Intracellular Side of the 5-HT3 Serotonin Receptor. ChemBioChem 6: 2180-2185. PMID: 16254942
79. Lomize MA, Pogozheva ID, Joo H, Mosberg HI, Lomize AL (2012) OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Research 40: D370-376. doi: 10.1093/nar/gkr703 PMID: 21890895
80. Jo S, Lim JB, Klauda JB, ImW(2009) CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes. Biophysical Journal 97: 50-58. doi: 10.1016/j.bpj.2009.04.013 PMID: 19580743
81. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. Journal of Molecular Graphics 14: 33-38, 27-28. PMID: 8744570
82. Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. Journal of Molecular Biology 234: 779-815. PMID: 8254673
83. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, et al. (2005) Scalable molecular dynamics with NAMD. Journal of Computational Chemistry 26: 1781-1802. PMID: 16222654
84. MacKerell AD, Bashford D, Bellott M, Dunbrack RL, Evanseck JD, Field MJ, et al. (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. The Journal of Physical Chemistry B 102: 3586-3616. doi: 10.1021/jp973084f PMID: 24889800
85. Caplan DA, Subbotina JO, Noskov SY (2008) Molecular Mechanism of Ion-Ion and Ion-Substrate Coupling in the Na+-Dependent Leucine Transporter LeuT. Biophysical Journal 95: 4613-4621. doi:10. 1529/biophysj.108.139741 PMID: 18708457
86. Noskov SY, Roux B (2008) Control of Ion Selectivity in LeuT: Two Na+ Binding Sites with Two Different Mechanisms. Journal of Molecular Biology 377: 804-818. doi: 10.1016/j.jmb.2008.01.015 PMID: 18280500
87. Klauda JB, Venable RM, Freites JA, O'Connor JW, Tobias DJ, Mondragon-Ramirez C, et al. (2010) Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types. The Journal of Physical Chemistry B 114: 7830-7843. doi: 10.1021/jp101759q PMID: 20496934
88. Darve E, Pohorille A (2001) Calculating free energies using average force. The Journal of Chemical Physics 115.
89. Darve E, Rodríguez-Gómez D, Pohorille A (2008) Adaptive biasing force method for scalar and vector free energy calculations. The Journal of Chemical Physics 128.
90. Hénin Jr, Fiorin G, Chipot C, Klein ML (2010) Exploring Multidimensional Free Energy Landscapes Using Time-Dependent Biases on Collective Variables. Journal of Chemical Theory and Computation 6: 35-47.
91. Smart OS, Neduvelil JG, Wang X, Wallace BA, Sansom MS (1996) HOLE: a program for the analysis of the pore dimensions of ion channel structural models. Journal of Molecular Graphics 14: 354-360, 376. PMID: 9195488
92. Yaffe E, Fishelovitch D, Wolfson HJ, Halperin D, Nussinov R (2008) MolAxis: a server for identification of channels in macromolecules. Nucleic Acids Research 36: W210-215. doi: 10.1093/nar/gkn223 PMID: 18448468
93. Roe DR, Cheatham TE (2013) PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data. Journal of Chemical Theory and Computation 9: 3084-3095.
94. Michaud-Agrawal N, Denning EJ, Woolf TB, Beckstein O (2011) MDAnalysis: A toolkit for the analysis of molecular dynamics simulations. Journal of Computational Chemistry 32: 2319-2327. doi: 10.1002/jcc.21787 PMID: 21500218
95. Baker NA, Sept D, Joseph S, Holst MJ, McCammon JA (2001) Electrostatics of nanosystems: application to microtubules and the ribosome. Proc Natl Acad Sci U S A 98: 10037-10041. PMID: 11517324
96. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. (2004) UCSF Chimera - a visualization system for exploratory research and analysis. Journal of Computational Chemistry 25: 1605-1612. PMID: 15264254
97. Hunter JD (2007) Matplotlib: A 2D Graphics Environment. Computing in Science & Engineering 9: 90-95.