Parametrization of macrolide antibiotics using the force field toolkit
© 2015 Wiley Periodicals, Inc.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 36(2015), 27 vom: 15. Okt., Seite 2052-63 |
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| Format: | Online-Aufsatz |
| Sprache: | English |
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2015
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Research Support, N.I.H., Extramural CHARMM parameters force field parametrization force field toolkit macrolides ribosome Amino Sugars Anti-Bacterial Agents Hexoses mehr... |
| Zusammenfassung: | © 2015 Wiley Periodicals, Inc. Macrolides are an important class of antibiotics that target the bacterial ribosome. Computer simulations of macrolides are limited as specific force field parameters have not been previously developed for them. Here, we determine CHARMM-compatible force field parameters for erythromycin, azithromycin, and telithromycin, using the force field toolkit (ffTK) plugin in VMD. Because of their large size, novel approaches for parametrizing them had to be developed. Two methods for determining partial atomic charges, from interactions with TIP3P water and from the electrostatic potential, as well as several approaches for fitting the dihedral parameters were tested. The performance of the different parameter sets was evaluated by molecular dynamics simulations of the macrolides in ribosome, with a distinct improvement in maintenance of key interactions observed after refinement of the initial parameters. Based on the results of the macrolide tests, recommended procedures for parametrizing very large molecules using ffTK are given |
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| Beschreibung: | Date Completed 16.06.2016 Date Revised 13.11.2018 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.24043 |