{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:58:38Z","timestamp":1777489118372,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009871","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000}}],"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["251247"],"award-info":[{"award-number":["251247"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["288008"],"award-info":[{"award-number":["288008"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1808716"],"award-info":[{"award-number":["1808716"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Spider venom GDPD-like phospholipases D (\n                    <jats:italic>SicTox<\/jats:italic>\n                    ) have been identified to be one of the major toxins in recluse spider venom. They are divided into two major clades: the \u03b1 clade and the \u03b2 clade. Most \u03b1 clade toxins present high activity against lipids with choline head groups such as sphingomyelin, while activities in \u03b2 clade toxins vary and include preference for substrates containing ethanolamine headgroups (\n                    <jats:italic>Sicarius terrosus<\/jats:italic>\n                    , St_\u03b2IB1). A structural comparison of available structures of phospholipases D (PLDs) reveals a conserved aromatic cage in the \u03b1 clade. To test the potential influence of the aromatic cage on membrane-lipid specificity we performed molecular dynamics (MD) simulations of the binding of several PLDs onto lipid bilayers containing choline headgroups; two\n                    <jats:italic>SicTox<\/jats:italic>\n                    from the \u03b1 clade,\n                    <jats:italic>Loxosceles intermedia<\/jats:italic>\n                    \u03b1IA1 (Li_\u03b1IA) and\n                    <jats:italic>Loxosceles laeta<\/jats:italic>\n                    \u03b1III1 (Ll_\u03b1III1), and one from the \u03b2 clade, St_\u03b2IB1. The simulation results reveal that the aromatic cage captures a choline-headgroup and suggest that the cage plays a major role in lipid specificity. We also simulated an engineered St_\u03b2IB1, where we introduced the aromatic cage, and this led to binding with choline-containing lipids. Moreover, a multiple sequence alignment revealed the conservation of the aromatic cage among the \u03b1 clade PLDs. Here, we confirmed that the i-face of \u03b1 and \u03b2 clade PLDs is involved in their binding to choline and ethanolamine-containing bilayers, respectively. Furthermore, our results suggest a major role in choline lipid recognition of the aromatic cage of the \u03b1 clade PLDs. The MD simulation results are supported by\n                    <jats:italic>in vitro<\/jats:italic>\n                    liposome binding assay experiments.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1009871","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T13:40:13Z","timestamp":1645191613000},"page":"e1009871","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Specificity of Loxosceles \u03b1 clade phospholipase D enzymes for choline-containing lipids: Role of a conserved aromatic cage"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9194-9881","authenticated-orcid":true,"given":"Emmanuel E.","family":"Moutoussamy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-2506","authenticated-orcid":true,"given":"Qaiser","family":"Waheed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greta J.","family":"Binford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5301-7234","authenticated-orcid":true,"given":"Hanif M.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9140-0522","authenticated-orcid":true,"given":"Shane M.","family":"Moran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-9259","authenticated-orcid":true,"given":"Anna R.","family":"Eitel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5763-1669","authenticated-orcid":true,"given":"Matthew H. J.","family":"Cordes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3649-7675","authenticated-orcid":true,"given":"Nathalie","family":"Reuter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"pcbi.1009871.ref001","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.toxicon.2016.08.002","article-title":"Description of Loxtox Protein Family and Identification of a new Group of Phospholipases D from Loxosceles Similis Venom Gland","volume":"120","author":"AE Dantas","year":"2016","journal-title":"Toxicon"},{"key":"pcbi.1009871.ref002","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.toxicon.2004.07.012","article-title":"Brown Spiders and Loxoscelism","volume":"44","author":"PH Da Silva","year":"2004","journal-title":"Toxicon"},{"key":"pcbi.1009871.ref003","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.toxicon.2013.01.027","article-title":"Modulation of Membrane Phospholipids, the Cytosolic Calcium Influx and Cell Proliferation Following Treatment of B16-F10 Cells with Recombinant Phospholipase-D from Loxosceles Intermedia (brown spider) venom.","volume":"67","author":"ACM Wille","year":"2013","journal-title":"Toxicon"},{"key":"pcbi.1009871.ref004","first-page":"767","article-title":"Phylogeny of Sicariidae spiders (Araneae: Haplogynae), with a monograph on Neotropical Sicarius","volume":"179","author":"IL Magalhaes","year":"2017","journal-title":"Zool J Linn Soc"},{"key":"pcbi.1009871.ref005","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1093\/molbev\/msn274","article-title":"Molecular Evolution, Functional Variation, and Proposed Nomenclature of the Gene Family that Includes Sphingomyelinase D in Sicariid Spider Venoms","volume":"26","author":"GJ Binford","year":"2009","journal-title":"Mol Biol Evol"},{"key":"pcbi.1009871.ref006","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1006\/bbrc.1998.9474","article-title":"Sphingomyelinases in the Venom of the Spider Loxosceles intermedia are Responsible for both Dermonecrosis and Complement-Dependent Hemolysis","volume":"251","author":"D V. Tambourgi","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"pcbi.1009871.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40409-017-0097-8","article-title":"Highlights in the Knowledge of Brown Spider Toxins.","volume":"23","author":"D Chaves-Moreira","year":"2017","journal-title":"J Venom Anim Toxins Incl Trop Dis."},{"key":"pcbi.1009871.ref008","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/jcb.25678","article-title":"Potential Implications for Designing Drugs Against the Brown Spider Venom Phospholipase-D","volume":"118","author":"D Chaves-Moreira","year":"2017","journal-title":"J Cell Biochem"},{"key":"pcbi.1009871.ref009","unstructured":"P.Gopalakrishnakone GC, Maria Elena de Lima E-G. Spider venoms. Springer; ISBN: 978-94-007-6388-3"},{"key":"pcbi.1009871.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0072372","article-title":"Phospholipase D Toxins of Brown Spider Venom Convert Lysophosphatidylcholine and Sphingomyelin to Cyclic Phosphates.","volume":"8","author":"DM Lajoie","year":"2013","journal-title":"PLoS One"},{"key":"pcbi.1009871.ref011","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.bbrc.2006.01.123","article-title":"Structural Insights Into the Catalytic Mechanism of Sphingomyelinases D and Evolutionary Relationship to Glycerophosphodiester Phosphodiesterases","volume":"342","author":"MT Murakami","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"pcbi.1009871.ref012","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.bbrc.2011.05.053","article-title":"Structure of a Novel Class II Phospholipase D: Catalytic Cleft is Modified by a Disulphide Bridge","volume":"409","author":"PO de Giuseppe","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"pcbi.1009871.ref013","doi-asserted-by":"crossref","first-page":"10994","DOI":"10.1074\/jbc.M115.636951","article-title":"Variable Substrate Preference Among Phospholipase D Toxins From Sicariid Spiders","volume":"290","author":"DM Lajoie","year":"2015","journal-title":"J Biol Chem"},{"key":"pcbi.1009871.ref014","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.toxicon.2009.02.013","article-title":"SMase II, a new sphingomyelinase D from Loxosceles laeta venom gland: Molecular cloning, expression, function and structural analysis","volume":"53","author":"GI de Santi Ferrara","year":"2009","journal-title":"Toxicon"},{"key":"pcbi.1009871.ref015","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.toxicon.2004.06.013","article-title":"Genetic and Enzymatic Characterization of Sphingomyelinase D Isoforms from the North American Fiddleback Spiders Loxosceles Boneti and Loxosceles Reclusa","volume":"44","author":"B Ramos-Cerrillo","year":"2004","journal-title":"Toxicon"},{"key":"pcbi.1009871.ref016","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.biochi.2006.12.002","article-title":"Two Novel Dermonecrotic Toxins LiRecDT4 and LiRecDT5 from Brown Spider (Loxosceles intermedia) Venom: From Cloning to Functional Characterization","volume":"89","author":"RB da Silveira","year":"2007","journal-title":"Biochimie"},{"key":"pcbi.1009871.ref017","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.toxicon.2006.04.010","article-title":"North and South American Loxosceles Spiders: Development of a Polyvalent Antivenom with Recombinant Sphingomyelinases D as Antigens","volume":"48","author":"A Olvera","year":"2006","journal-title":"Toxicon"},{"key":"pcbi.1009871.ref018","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.biochi.2006.02.008","article-title":"Molecular cloning and functional characterization of two isoforms of dermonecrotic toxin from Loxosceles intermedia (Brown spider) venom gland.","volume":"88","author":"R Bertoni da Silveira","year":"2006","journal-title":"Biochimie"},{"key":"pcbi.1009871.ref019","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.toxicon.2012.04.350","article-title":"Sphingomyelinase D in Sicariid Spider Venom is a Potent Insecticidal Toxin","volume":"60","author":"PA Zobel-Thropp","year":"2012","journal-title":"Toxicon"},{"key":"pcbi.1009871.ref020","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.bpj.2016.02.020","article-title":"A Role for Weak Electrostatic Interactions in Peripheral Membrane Protein Binding","volume":"110","author":"HM Khan","year":"2016","journal-title":"Biophys J"},{"key":"pcbi.1009871.ref021","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1016\/j.bbamem.2014.09.003","article-title":"Two Homologous Neutrophil Serine Proteases Bind to POPC Vesicles with Different Affinities: When Aromatic Amino Acids 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Grauffel","year":"2013","journal-title":"J Am Chem Soc"},{"key":"pcbi.1009871.ref025","doi-asserted-by":"crossref","first-page":"8435","DOI":"10.1021\/acs.chemrev.8b00208","article-title":"Search and Subvert: Minimalist Bacterial Phosphatidylinositol-Specific Phospholipase C Enzymes","volume":"118","author":"MF Roberts","year":"2018","journal-title":"Chem Rev"},{"key":"pcbi.1009871.ref026","doi-asserted-by":"crossref","first-page":"14863","DOI":"10.1074\/jbc.M113.466532","article-title":"The Cation-\u03c0 Box Is a Specific Phosphatidylcholine Membrane Targeting Motif*","volume":"288","author":"J Cheng","year":"2013","journal-title":"J Biol Chem"},{"key":"pcbi.1009871.ref027","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.1021\/acs.jpclett.9b01639","article-title":"Interfacial Aromatics Mediating Cation-\u03c0Interactions with Choline-Containing Lipids Can Contribute as Much to Peripheral Protein Affinity for Membranes as Aromatics Inserted below the Phosphates","volume":"10","author":"Q Waheed","year":"2019","journal-title":"J Phys Chem Lett"},{"key":"pcbi.1009871.ref028","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S0896-6273(04)00115-1","article-title":"Nicotine and Carbamylcholine Binding to Nicotinic Acetylcholine Receptors as Studied in AChBP Crystal Structures","volume":"41","author":"PH Celie","year":"2004","journal-title":"Neuron"},{"key":"pcbi.1009871.ref029","first-page":"507","article-title":"Structure of Human Phosphatidylcholine Transfer Protein in Complex with its Ligand","volume":"9","author":"SL Roderick","year":"2002","journal-title":"Nat Struct Biol"},{"key":"pcbi.1009871.ref030","article-title":"Cation-\u03c0 Interactions in Ligand Recognition by Serotonergic (5-HT3A) and Nicotinic Acetylcholine Receptors: The Anomalous Binding Properties of Nicotine","author":"DL Beene","year":"2002","journal-title":"Biochemistry"},{"key":"pcbi.1009871.ref031","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1107\/S0907444902003451","article-title":"The Protein Data Bank","volume":"58","author":"HM Berman","year":"2002","journal-title":"Acta Crystallogr Sect D Biol Crystallogr"},{"key":"pcbi.1009871.ref032","first-page":"559","article-title":"MUSTANG: A multiple structural alignment algorithm","volume":"64","author":"S. K Arun","year":"2006","journal-title":"Sci Technol"},{"key":"pcbi.1009871.ref033","doi-asserted-by":"crossref","first-page":"W636","DOI":"10.1093\/nar\/gkz268","article-title":"The EMBL-EBI Search and Sequence Analysis Tools APIs in 2019","volume":"47","author":"F Madeira","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009871.ref034","first-page":"859","article-title":"Software News and Updates CHARMM-GUI: A Web-Based Graphical User Interface for CHARMM","volume":"29","author":"Sunhwan Jo","year":"2008","journal-title":"J Comput Chem"},{"key":"pcbi.1009871.ref035","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1002\/jcc.23702","article-title":"CHARMM-GUI Membrane Builder Toward Realistic Biological Membrane Simulations","volume":"35","author":"EL Wu","year":"2014","journal-title":"J Comput Chem"},{"key":"pcbi.1009871.ref036","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bpj.2009.04.013","article-title":"CHARMM-GUI Membrane Builder for Mixed Bilayers and its Application to Yeast Membranes","volume":"97","author":"S Jo","year":"2009","journal-title":"Biophys J"},{"key":"pcbi.1009871.ref037","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1021\/acs.jctc.8b01066","article-title":"CHARMM-GUI Membrane Builder for Complex Biological Membrane Simulations with Glycolipids and Lipoglycans","volume":"15","author":"J Lee","year":"2019","journal-title":"J Chem Theory Comput"},{"key":"pcbi.1009871.ref038","doi-asserted-by":"crossref","first-page":"7830","DOI":"10.1021\/jp101759q","article-title":"Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types","volume":"114","author":"JB Klauda","year":"2010","journal-title":"J Phys Chem B"},{"key":"pcbi.1009871.ref039","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1021\/ct300400x","article-title":"Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone \u03c6, \u03c8 and Side-Chain \u03c71 and \u03c72 Dihedral Angles","volume":"8","author":"RB Best","year":"2012","journal-title":"J Chem Theory Comput"},{"key":"pcbi.1009871.ref040","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1021\/jp973084f","article-title":"All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins","volume":"102","author":"AD MacKerell","year":"1998","journal-title":"J Phys Chem B"},{"key":"pcbi.1009871.ref041","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00232-005-7006-8","article-title":"Structure of Fully Hydrated Fluid Phase Lipid Bilayers with Monounsaturated Chains","volume":"208","author":"N Ku\u010derka","year":"2006","journal-title":"J Membr Biol"},{"key":"pcbi.1009871.ref042","doi-asserted-by":"crossref","first-page":"8000","DOI":"10.1038\/s41598-019-44318-9","article-title":"Role of Lipid Composition on the Structural and Mechanical Features of Axonal Membranes: A Molecular Simulation Study","volume":"9","author":"M Saeedimasine","year":"2019","journal-title":"Sci Rep"},{"key":"pcbi.1009871.ref043","doi-asserted-by":"crossref","first-page":"15318","DOI":"10.1021\/bi048231w","article-title":"Molecular-Level Organization of Saturated and Polyunsaturated Fatty Acids in a Phosphatidylcholine Bilayer Containing Cholesterol","volume":"43","author":"MC Pitman","year":"2004","journal-title":"Biochemistry"},{"key":"pcbi.1009871.ref044","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A Visualization System for Exploratory Research and Analysis","volume":"25","author":"EF Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"pcbi.1009871.ref045","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1093\/nar\/gkr703","article-title":"OPM Database and PPM Web Server: Resources for Positioning of Proteins in Membranes","volume":"40","author":"MA Lomize","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009871.ref046","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"W Humphrey","year":"1996","journal-title":"J Mol Graph"},{"key":"pcbi.1009871.ref047","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1021\/ct200133y","article-title":"Improved Treatment of Ligands and Coupling Effects in Empirical Calculation and Rationalization of pKa Values","volume":"7","author":"CR S\u00f8ndergaard","year":"2011","journal-title":"J Chem Theory Comput"},{"key":"pcbi.1009871.ref048","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa Predictions.","volume":"7","author":"MHM Olsson","year":"2011","journal-title":"J Chem Theory Comput."},{"key":"pcbi.1009871.ref049","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable Molecular Dynamics with NAMD","volume":"26","author":"JC Phillips","year":"2005","journal-title":"J Comput Chem"},{"key":"pcbi.1009871.ref050","doi-asserted-by":"crossref","first-page":"5585","DOI":"10.1021\/acs.jctc.6b00654","article-title":"Improving the Force Field Description of Tyrosine-Choline Cation-\u03c0 Interactions: QM Investigation of Phenol-N(Me)4+ Interactions","volume":"12","author":"HM Khan","year":"2016","journal-title":"J Chem Theory Comput"},{"key":"pcbi.1009871.ref051","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1021\/acs.jctc.8b00839","article-title":"Cation-\u03c0 Interactions between Methylated Ammonium Groups and Tryptophan in the CHARMM36 Additive Force Field","volume":"15","author":"HM Khan","year":"2019","journal-title":"J Chem Theory Comput"},{"key":"pcbi.1009871.ref052","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s00214-018-2376-z","article-title":"Modeling Induction Phenomena in Amino Acid Cation\u2013\u03c0 Interactions","volume":"137","author":"CR Rupakheti","year":"2018","journal-title":"Theor Chem Acc"},{"key":"pcbi.1009871.ref053","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/0021-9991(83)90014-1","article-title":"Rattle: A \u201cVelocity\u201d Version of the Shake Algorithm for Molecular Dynamics Calculations.","volume":"52","author":"HC Andersen","year":"1983","journal-title":"J Comput Phys"},{"key":"pcbi.1009871.ref054","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A Smooth Particle Mesh Ewald Method","volume":"103","author":"U Essmann","year":"1995","journal-title":"J Chem Phys"},{"key":"pcbi.1009871.ref055","doi-asserted-by":"crossref","first-page":"10183","DOI":"10.1021\/jp401512z","article-title":"Simulations of Anionic Lipid Membranes: Development of Interaction-Specific Ion Parameters and Validation Using NMR data","volume":"117","author":"RM Venable","year":"2013","journal-title":"J Phys Chem B"},{"key":"pcbi.1009871.ref056","first-page":"1545","article-title":"CHARMM: Molecular Dynamics Simulation Package","volume":"30","author":"BR Brooks","year":"2009","journal-title":"J Comput Chem"},{"key":"pcbi.1009871.ref057","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"W Humphrey","year":"1996","journal-title":"J Mol Graph"},{"key":"pcbi.1009871.ref058","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1002\/jcc.21787","article-title":"Beckstein. MDAnalysis: A Toolkit for the Analysis of Molecular Dynamics Simulations","volume":"32","author":"E. J. Michaud-Agrawal N","year":"2011","journal-title":"Comput Chem"},{"key":"pcbi.1009871.ref059","doi-asserted-by":"crossref","unstructured":"Gowers R, Linke M, Barnoud J, Reddy T, Melo M, Seyler S, et al. MDAnalysis: A Python Package for the Rapid Analysis of Molecular Dynamics Simulations. 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