In silico screening and epitope mapping of leptospiral outer membrane protein—Lsa46

Abstract

Leptospirosis is one of the neglected diseases caused by the spirochete, Leptospira interrogans. Leptospiral surface adhesion (Lsa) proteins are surface exposed outer membrane proteins present in the pathogen. It acts as laminin and plasminogen binding proteins which enable them to infect host cells. The major target for the development of vaccine in the current era focuses on surface exposed outer membrane proteins, as they can induce strong and fast immune response in hosts. Therefore, the present study mapped the potential epitopes of the Leptospiral outer membrane proteins, mainly the surface adhesion proteins. Protein sequence analysis of Lsa proteins was done by in silico methods. The primary protein sequence analysis revealed Lsa46 as a suitable target which can be a potent Leptospiral vaccine candidate. Its structure was modelled by threading based method in I-TASSER server and validated by Ramachandran plot. The predicted epitope’s interactions with human IgG, IgM(Fab) and T-cell receptor TCR(αβ) were performed by molecular docking studies using Biovia Discovery studio 2018. One of the predicted B-cell epitopes and the IgG showed desirable binding interactions, while four of the predicted B-cell epitopes and T-cell epitopes showed desirable binding interactions with IgM and TCR respectively. The molecular dynamic simulation studies carried out with the molecular docked complexes gave minimized energies indicating stable interactions. The structural analysis of the entire simulated complex showed a stable nature except for one of the Epitope-IgM complex. Further the binding free energy calculation of eight receptor-ligand complex predicted them energetically stable. The results of the study help in elucidating the structural and functional characterization of Lsa46 for epitope-based vaccine design.

Communicated by Ramaswamy H. Sarma.

Keywords:

• Leptospirosis
• outer membrane protein
• epitope
• molecular docking
• immunoinformatics

Authors’ contributions

J.M.I.: conceived the study, designed the study, data analysis, writing and drafting the manuscript. S.A.: coordinated the study. P.R.S., A.S.N. and O.V.O.: designed the study, data analysis, coordinated the study, revised and proof read the draft manuscript. All authors read and approved the final manuscript.

Acknowledgement

The authors acknowledge the SIUCEB support at the Department of Computational Biology and Bioinformatics, University of Kerala, India for providing the necessary facilities to carry out this study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was funded by University of Kerala, by way of a fellowship to JMI. PRS was supported by ISCA, Kolkata by Asutosh Mookerjee Fellowship.