In-silico screening and identification of potential inhibitors against 2Cys peroxiredoxin of Candidatus Liberibacter asiaticus

Abstract

Huanglongbing (HLB) is a worldwide citrus plant disease-related to non-culturable and fastidious α-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.

Communicated by Ramaswamy H. Sarma

Keywords:

• Peroxiredoxin
• Candidatus Liberibacter asiaticus
• oxidative stress
• quantum mechanics
• molecular dynamics simulation

Acknowledgments

We are thankful to the Department of chemistry, IIT Roorkee, to provide the Gaussian software. Authors thank Macromolecular Crystallographic Unit (MCU), a Central Facility at Institute Instrumentation Centre (IIC), IIT Roorkee, for computational work. Authors acknowledge Prof. Shailly Tomar, IIT Roorkee, for providing the computational facility.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a grant No. BT/PR9877/BRB/10/1274/2014 from Department of Biotechnology, Ministry of Science and Technology, Government of India. DNG, VD, BKS, and PD thank University Grant Commission (UGC), Department of Biotechnology [DBT/2015/IIT-R/349], Council of Scientific & Industrial Research (CSIR), and Ministry of Human Resource Development (MHRD) for financial support.