{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T17:10:31Z","timestamp":1776013831888,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"publisher","award":["OTKA K-128659"],"award-info":[{"award-number":["OTKA K-128659"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>We previously reported on a novel peptaibol, named Tripleurin XIIc (TPN), an 18-residue long sequence produced by the fungus Trichoderma pleuroti. We elucidated its 3D structure via classical and accelerated molecular dynamics simulation (aMD) methods and reported the folding dynamics of TPN in water and chloroform solvents. Peptaibols, in general, are insoluble in water, as they are amphipathic and may prefer hydrophobic environments like transmembrane regions. In this study, we attempted to use aMD simulations to model an all-atom bacterial membrane system while placing a TPN molecule in its vicinity. The results highlighted that TPN was able to introduce some disorder into the membrane and caused lipid clustering. It could also enter the transmembrane region from the water-bilayer interface. The structural dynamics of TPN in the transmembrane region revealed a single energetically stable conformation similar to the one obtained from water and chloroform solvent simulations reported by us previously. However, this linear structure was found to be at the local energy minimum (stable) in water but at a metastable intermediate state (higher energy) in chloroform. Therefore, it could be said that the water solvent can be successfully used for folding simulations of peptaibols.<\/jats:p>","DOI":"10.3390\/life13122288","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T07:44:42Z","timestamp":1701330282000},"page":"2288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modeling the Effect on a Novel Fungal Peptaibol Placed in an All-Atom Bacterial Membrane Mimicking System via Accelerated Molecular Dynamics Simulations"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7067-4770","authenticated-orcid":false,"given":"Chetna","family":"Tyagi","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"Marik","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1651-4623","authenticated-orcid":false,"given":"Andr\u00e1s","family":"Szekeres","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-7773","authenticated-orcid":false,"given":"Csaba","family":"V\u00e1gv\u00f6lgyi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-3973","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Kredics","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7630-5466","authenticated-orcid":false,"given":"Ferenc","family":"\u00d6tv\u00f6s","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Biological Research Centre, Temesv\u00e1ri krt. 62, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7951","DOI":"10.1073\/pnas.79.24.7951","article-title":"Peptaibol antibiotics: A study on the helical structure of the 2-9 sequence of emerimicins III and IV","volume":"79","author":"Benedetti","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1007\/BF01965190","article-title":"Paracelsin, a peptide antibiotic containing \u03b1-aminoisobutyric acid, isolated from Trichoderma reesei Simmons Part A","volume":"39","author":"Graf","year":"1983","journal-title":"Experientia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1002\/cbdv.200890171","article-title":"Peptaibiomics: Towards a myriad of bioactive peptides containing C\u03b1-dialkylamino acids?","volume":"5","author":"Degenkolb","year":"2008","journal-title":"Chem. Biodivers."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0065-2911(08)60156-3","article-title":"Thiol template peptide synthesis systems in bacteria and fungi","volume":"Volume 38","author":"Poole","year":"1996","journal-title":"Advances in Microbial Physiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1021\/cr960029e","article-title":"Modular peptide synthetases involved in nonribosomal peptide synthesis","volume":"97","author":"Marahiel","year":"1997","journal-title":"Chem. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1139\/w05-006","article-title":"Multiple non-ribosomal peptide synthetase genes determine peptaibol synthesis in Trichoderma virens","volume":"51","author":"Wei","year":"2005","journal-title":"Can. J. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Marik, T., Urb\u00e1n, P., Tyagi, C., Szekeres, A., Leitgeb, B., V\u00e1gv\u00f6lgyi, M., Manczinger, L., Druzhinina, I., V\u00e1gv\u00f6lgyi, C., and Kredics, L. (2017). Diversity profile and dynamics of peptaibols produced by green mould Trichoderma species in interactions with their hosts Agaricus bisporus and Pleurotus ostreatus. Chem. Biodivers., 14.","DOI":"10.1002\/cbdv.201700033"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tyagi, C., Marik, T., V\u00e1gv\u00f6lgyi, C., Kredics, L., Szekeres, A., and \u00d6tv\u00f6s, F. (2019). Tripleurin XIIc: Peptide folding dynamics in aqueous and hydrophobic environment mimic using accelerated molecular dynamics. Molecules, 24.","DOI":"10.3390\/molecules24020358"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6164","DOI":"10.1021\/acs.langmuir.5b01011","article-title":"Atomic force microscopy reveals the mechanobiology of lytic peptide action on bacteria","volume":"31","author":"Mularski","year":"2015","journal-title":"Langmuir"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8553","DOI":"10.1021\/acs.jpcb.5b03133","article-title":"Small-anion selective transmembrane \u201choles\u201d induced by an antimicrobial peptide too short to span membranes","volume":"119","author":"Hu","year":"2015","journal-title":"J. Phys. Chem. B"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9678","DOI":"10.1021\/acs.jpcb.5b04543","article-title":"Thermodynamic and biophysical analysis of the membrane-association of a histidine-rich peptide with efficient antimicrobial and transfection activities","volume":"119","author":"Voievoda","year":"2015","journal-title":"J. Phys. Chem. B"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11856","DOI":"10.1021\/bi980539y","article-title":"Relationship of membrane curvature to the formation of pores by magainin 2","volume":"37","author":"Matsuzaki","year":"1998","journal-title":"Biochemistry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.chemphyslip.2011.12.005","article-title":"Effect of head group and curvature on binding of the antimicrobial peptide tritrpticin to lipid membranes","volume":"165","author":"Bozelli","year":"2012","journal-title":"Chem. Phys. Lipids"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1016\/j.bbamem.2014.05.013","article-title":"The role of spontaneous lipid curvature in the interaction of interfacially active peptides with membranes","volume":"1838","author":"Koller","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00232-014-9733-1","article-title":"The curvature induction of surface-bound antimicrobial peptides piscidin 1 and piscidin 3 varies with lipid chain length","volume":"248","author":"Perrin","year":"2015","journal-title":"J. Membr. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14346","DOI":"10.1021\/ja8062327","article-title":"Bacterial membranes as predictors of antimicrobial potency","volume":"130","author":"Epand","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1128\/AAC.00321-09","article-title":"Lipid segregation explains selective toxicity of a series of fragments derived from the human cathelicidin LL-37","volume":"53","author":"Epand","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/psc.1319","article-title":"Bacterial membrane lipids in the action of antimicrobial agents","volume":"17","author":"Epand","year":"2011","journal-title":"J. Pept. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.bbamem.2015.10.018","article-title":"Molecular mechanisms of membrane targeting antibiotics","volume":"1858","author":"Epand","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1021\/bi015841c","article-title":"Specific binding of Ro 09-0198 (cinnamycin) to phosphatidylethanolamine: A thermodynamic analysis","volume":"41","author":"Machaidze","year":"2002","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4494","DOI":"10.1128\/JB.00011-12","article-title":"Daptomycin-mediated reorganization of membrane architecture causes mislocalization of essential cell division proteins","volume":"194","author":"Pogliano","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1016\/0960-894X(96)00410-6","article-title":"Ion channel-forming property of trichorovin-XII, an 11-residue peptaibol from the fungus Trichoderma viride, in planar lipid bilayer membranes","volume":"6","author":"Wada","year":"1996","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","unstructured":"Tyagi, C. (2020). Structural Investigation of Peptaibols Using Accelerated Molecular Dynamics Simulations. [Ph.D. Thesis, University of Szeged]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1039\/D0FD00041H","article-title":"Antimicrobial peptides: Mechanism of action and lipid-mediated synergistic interactions within membranes","volume":"232","author":"Juhl","year":"2021","journal-title":"Faraday Discuss."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D555","DOI":"10.1093\/nar\/gkw960","article-title":"The antiSMASH database, a comprehensive database of microbial secondary metabolite biosynthetic gene clusters","volume":"45","author":"Blin","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1021\/acs.jcim.9b00269","article-title":"PACKMOL-Memgen: A simple-to-use, generalized workflow for membrane-protein\u2013lipid-bilayer system building","volume":"59","author":"Gohlke","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"ref_27","unstructured":"Case, D., Ben-Shalom, I., Brozell, S., Cerutti, D., Cheatham, T., Cruzeiro, V., Darden, T., Duke, R., Ghoreishi, D., and Gilson, M. (2018). AMBER 18, University of California."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N\u22c5log (N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1002\/jcc.20482","article-title":"Software news and updates. Carma: A molecular dynamics analysis program","volume":"27","author":"Glykos","year":"2006","journal-title":"J. Comput. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1002\/jcc.23381","article-title":"Grcarma: A fully automated task-oriented interface for the analysis of molecular dynamics trajectories","volume":"34","author":"Koukos","year":"2013","journal-title":"J. Comput. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1021\/ct500090q","article-title":"Improved reweighting of accelerated molecular dynamics simulations for free energy calculation","volume":"10","author":"Miao","year":"2014","journal-title":"J. Chem. Theory Comput."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1063\/1.455219","article-title":"A simulation-based model of NMR T 1 relaxation in lipid bilayer vesicles","volume":"89","author":"Pastor","year":"1988","journal-title":"J. Chem. Phys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1073\/pnas.88.3.892","article-title":"Model for the structure of the lipid bilayer","volume":"88","author":"Pastor","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.chemphyslip.2015.07.014","article-title":"Mechanical properties of lipid bilayers from molecular dynamics simulation","volume":"192","author":"Venable","year":"2015","journal-title":"Chem. Phys. Lipids"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tyagi, C., Marik, T., V\u00e1gv\u00f6lgyi, C., Kredics, L., and \u00d6tv\u00f6s, F. (2019). Accelerated molecular dynamics applied to the peptaibol folding problem. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174268"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23635","DOI":"10.1039\/C8CP04278K","article-title":"Molecular dynamics modeling of Pseudomonas aeruginosa outer membranes","volume":"20","author":"Li","year":"2018","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10289","DOI":"10.1021\/acs.langmuir.3c00538","article-title":"In Search of a Molecular View of Peptide\u2013Lipid Interactions in Membranes","volume":"39","author":"Almeida","year":"2023","journal-title":"Langmuir"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/S0076-6879(98)95035-2","article-title":"Energetics of Peptide\u2013Bilayer Interactions","volume":"295","author":"White","year":"1998","journal-title":"Meth. Enzymol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.bbamem.2011.07.019","article-title":"Hydrogen-bond energetics drive helix formation in membrane interfaces","volume":"1818","author":"Almeida","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"De Zotti, M., Sella, L., Bolzonello, A., Gabbatore, L., Peggion, C., Bortolotto, A., Elmaghraby, I., Tundo, S., and Favaron, F. (2020). Targeted amino acid substitutions in a Trichoderma peptaibol confer activity against fungal plant pathogens and protect host tissues from Botrytis cinerea infection. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207521"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"881961","DOI":"10.3389\/fpls.2022.881961","article-title":"Water-soluble Trichogin GA IV-derived peptaibols protect tomato plants from Botrytis cinerea infection with limited impact on plant defenses","volume":"13","author":"Baccelli","year":"2022","journal-title":"Front. Plant. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"011103","DOI":"10.1063\/1.4973703","article-title":"Communication: Alamethicin can capture lipid-like molecules in the membrane","volume":"146","author":"Afanasyeva","year":"2017","journal-title":"J. Chem. Phys."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.jelechem.2017.10.042","article-title":"In situ electrochemical and PM-IRRAS studies of alamethicin ion channel formation in model phospholipid bilayers","volume":"819","author":"Su","year":"2018","journal-title":"J. Electroanal. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1016\/j.bpj.2017.05.019","article-title":"Structural behavior of the peptaibol harzianin HK VI in a DMPC bilayer: Insights from MD simulations","volume":"112","author":"Putzu","year":"2017","journal-title":"Biophys. J."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Finger, S., Kerth, A.M., Dathe, M., and Blume, A. (2020). The impact of non-ideality of lipid mixing on peptide induced lipid clustering. Biochim. Biophys. Acta (BBA)-Biomembr., 1862.","DOI":"10.1016\/j.bbamem.2020.183248"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/12\/2288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:34:42Z","timestamp":1760132082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/12\/2288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,30]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["life13122288"],"URL":"https:\/\/doi.org\/10.3390\/life13122288","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,30]]}}}