In-silico screening and identification of potential inhibitors against 2Cys peroxiredoxin of Candidatus Liberibacter asiaticus
In-silico screening and identification of potential inhibitors against 2Cys peroxiredoxin of Candidatus Liberibacter asiaticus
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DOI：
10.1080/07391102.2021.1916597
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发表时间：
2021-04-12
影响因子：
4.4
通讯作者：
Sharma, Ashwani Kumar
中科院分区：
文献类型：
--
作者：
Gupta, Deena Nath;Dalal, Vikram;Sharma, Ashwani Kumar
Huanglongbing (HLB) is a worldwide citrus plant disease-related to non-culturable and fastidious alpha-proteobacteria Candidatus Liberibacter asiaticus (CLas). In CLas, Peroxiredoxin (Prx) plays a major role in the reduction of the level of reactive species such as reactive oxygen species (ROS), free radicals and peroxides, etc. Here, we have used structure-based drug designing approach was used to screen and identify the potent molecules against 2Cys Prx. The virtual screening of fragments library was performed against the three-dimensional validated model of Prx. To evaluate the binding affinity, the top four molecules (N-Boc-2-amino isobutyric acid (B2AI), BOC-L-Valine (BLV), 1-(boc-amino) cyclobutane carboxylic acid (1BAC), and N-Benzoyl-DL-alanine (BDLA)) were docked at the active site of Prx. The molecular docking results revealed that all the identified molecules had a higher binding affinity than Tert butyl hydroperoxide (TBHP), a substrate of Prx. Molecular dynamics analysis such as RMSD, Rg, SASA, hydrogen bonds, and PCA results indicated that Prx-inhibitor(s) complexes had lesser fluctuations and were more stable and compact than Prx-TBHP complex. MMPBSA results confirmed that the identified compounds could bind at the active site of Prx to form a lower energy Prx-inhibitor(s) complex than Prx-TBHP complex. The identified potent molecules may pave the path for the development of antimicrobial agents against CLA.
