期刊
CELL BIOCHEMISTRY AND BIOPHYSICS
卷 76, 期 3, 页码 391-400出版社
HUMANA PRESS INC
DOI: 10.1007/s12013-018-0846-5
关键词
Acinetobacter baumannii; AdeABC efflux pump; Microbial drug resistance; Virtual screening; Molecular dynamics simulation; Outer membrane protein
资金
- Central University of Rajasthan
- SERB India
The structure and functioning of multidrug efflux systems provide us with a better understanding of the transport of various antibiotics, thus giving a path for the discovery of effective compounds for combating the multidrug resistance in Acinetobacter baumannii. In the present study, a number of computational techniques have been used to search for an inhibitor for the RND efflux pump, AdeABC, of A. baumannii targeting specifically its outermost component, i.e., AdeC. We have prepared the three-dimensional structure for AdeC using MODELLER v9.16 and identified its active binding site using SiteMap. Using high-throughput virtual screening, we identified compounds from a large library of biogenic compounds on the basis of their effective interaction at the binding site of AdeC. The validation of docking step was performed by plotting ROC curve (enrichment calculations). The docked complexes were further analyzed for their binding free energies by molecular mechanics using Generalized Born model and Solvent Accessibility (MMGBSA). The molecular dynamics simulation was performed for AdeC-ZINC77257599 complex using GROMACS. The present rational drug designing, molecular mechanics and molecular dynamics data provided an inhibitor, i.e, ZINC77257599 [(3R,4Z,6E,8E)-3-hydroxy-2,2,4-trimethyl-10-oxazol-5-yl-deca-4,6,8-trienamide], for the outer membrane protein component (AdeC) of efflux pump AdeABC of A. baumannii.
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