Publication:
Comparative molecular dynamics simulations of amphotericin B-cholesterol/ergosterol membrane channels

dc.contributor.coauthorBaginski, Maciej
dc.contributor.coauthorBorowski, Edward
dc.contributor.departmentDepartment of Physics
dc.contributor.kuauthorReşat, Haluk
dc.contributor.schoolcollegeinstituteCollege of Sciences
dc.date.accessioned2024-11-09T23:49:11Z
dc.date.issued2002
dc.description.abstractAmphotericin B (AmB) is a very effective anti-fungal polyene macrolide antibiotic whose usage is limited by its toxicity. Lack of a complete understanding of AmB's molecular mechanism has impeded attempts to design less toxic AmB derivatives. The antibiotic is known to interact with sterols present in the cell membrane to form ion channels that disrupt membrane function. The slightly higher affinity of AmB toward ergosterol (dominant sterol in fungal cells) than cholesterol (mammalian sterol) is regarded as the most essential factor on which antifungal chemotherapy is based. To study these differences at the molecular level, two realistic model membrane channels containing molecules of AmB, sterol (cholesterol or ergosterol), phospholipid, and water were studied by molecular dynamics (MID) simulations. Comparative analysis of the simulation data revealed that the sterol type has noticeable effect on the properties of AmB membrane channels. In addition to having a larger size, the AmB channel in the ergosterol-containing membrane has a more pronounced pattern of intermolecular hydrogen bonds. The interaction between the antibiotic and ergosterol is more specific than between the antibiotic and cholesterol. These observed differences suggest that the channel in the ergosterol-containing membrane is more stable and, due to its larger size, would have a higher ion conductance. These observations are in agreement with experiments. (C) 2002 Elsevier Science B.V. All rights reserved.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.issue44958
dc.description.openaccessNO
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.volume1567
dc.identifier.doi10.1016/S0005-2736(02)00581-3
dc.identifier.eissn0006-3002
dc.identifier.issn0005-2736
dc.identifier.quartileQ2
dc.identifier.scopus2-s2.0-0344291484
dc.identifier.urihttps://doi.org/10.1016/S0005-2736(02)00581-3
dc.identifier.urihttps://hdl.handle.net/20.500.14288/14331
dc.identifier.wos180323100009
dc.keywordsAmphotericin B
dc.keywordsCholesterol
dc.keywordsErgosterol
dc.keywordsPhospholipid
dc.keywordsMolecular modeling
dc.keywordsIon channel
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofBiochimica Et Biophysica Acta-Biomembranes
dc.subjectBiochemistry and molecular biology
dc.subjectBiophysics
dc.titleComparative molecular dynamics simulations of amphotericin B-cholesterol/ergosterol membrane channels
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorReşat, Haluk
local.publication.orgunit1College of Sciences
local.publication.orgunit2Department of Physics
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