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Molecular dynamics simulations suggest why the A2058G mutation in 23S RNA results in bacterial resistance against clindamycin

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cris.lastimport.scopus2024-02-12T20:37:30Z
dc.abstract.enClindamycin, a lincosamide antibiotic, binds to 23S ribosomal RNA and inhibits protein synthesis. The A2058G mutation in 23S RNA results in bacterial resistance to clindamycin. To understand the influence of this mutation on short-range interactions of clindamycin with 23S RNA, we carried out full-atom molecular dynamics simulations of a ribosome fragment containing clindamycin binding site. We compared the dynamical behavior of this fragment simulated with and without the A2058G mutation. Molecular dynamics simulations suggest that clindamycin in the native ribosomal binding site is more internally flexible than in the A2058G mutant. Only in the native ribosome fragment did we observe intramolecular conformational change of clindamycin around its C7-N1-C10-C11 dihedral. In the mutant, G2058 makes more stable hydrogen bonds with clindamycin hindering its conformational freedom in the ribosome-bound state. Clindamycin binding site is located in the entrance to the tunnel through which the newly synthesized polypeptide leaves the ribosome. We observed that in the native ribosome fragment, clindamycin blocks the passage in the tunnel entrance, whereas in the mutated fragment the aperture is undisturbed due to a different mode of binding of clindamycin in the mutant. Restricted conformational freedom of clindamycin in a position not blocking the tunnel entrance in the A2058G mutant could explain the molecular mechanism of bacterial resistance against clindamycin occurring in this mutant.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorTrylska, Joanna
dc.contributor.authorKulczycka-Mierzejewska, Katarzyna
dc.contributor.authorSadlej, Joanna
dc.date.accessioned2024-01-25T12:53:13Z
dc.date.available2024-01-25T12:53:13Z
dc.date.issued2018
dc.description.financeNie dotyczy
dc.description.number9
dc.description.volume24
dc.identifier.doi10.1007/S00894-018-3689-5
dc.identifier.issn1610-2940
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/112859
dc.languageeng
dc.pbn.affiliationphysical sciences
dc.relation.ispartofJournal of Molecular Modeling
dc.relation.pages91
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.en2018 Trylska
dc.titleMolecular dynamics simulations suggest why the A2058G mutation in 23S RNA results in bacterial resistance against clindamycin
dc.typeJournalArticle
dspace.entity.typePublication