Transferrin binding protein-B from Neisseria meningitidis C as a novel carrier protein in glycoconjugate preparation: an in silico approach

Abstract

The linking of polysaccharide in glycoconjugate vaccine with carrier protein is an imperative step to develop a strong memory response. The excessive use of similar carrier protein known to result in bystander immunity warrants an urgent need for new carrier protein. The preparation of the glycoconjugate vaccine using cyanylation chemistry is to link the active cyanate ester site of polysaccharide with the carrier protein. In the present study, transferrin binding protein-B (Tbp-B) has been explored as a new carrier protein to develop in silico pneumococcal polysaccharide serotype-5 (PnPs-5) conjugate vaccine. The homology model of Tbp-B was constructed using the Prime module and stereochemically validated using ProSA, PDBsum and ProQ. The selected model revealed a Z-score of −5.6 within the X-ray region in ProSA analysis, LGscore: 9.776, and MaxSub: 0.8 in protein quality predictor suggesting its preferred use. Loop modeling and active site analysis followed by in silico PnPs-5 activation with cyanalyting agent CDAP was docked with Tbp-B using Glide module. The complex stability of cyanate esters with Tbp-B, analyzed by molecular dynamics (MD) simulation, revealed an average RMSD of 2.49 Å for its binding to the receptor. The RMSF values of cyanate ester-1, -2, and -3 were observed to be 1.06, 1.39 and 0.79 Å, respectively. The higher RMSF of 1.39 Å of cyanate ester-2 was further found unstable which corroborates its non-binding to the protein and also incurring conformational changes to a carrier protein. Molecular simulations revealed that cyanate ester-1 and cyanate ester-3 formed stable conjugates with carrier protein Tbp-B.

Communicated by Ramaswamy H. Sarma

Keywords:

• Conjugate vaccine
• transferrin binding protein-B
• molecular docking
• molecular dynamic simulation

Acknowledgements

The authors are thankful to Dr. Cyrus Poonawalla and Mr. Adar Poonawalla (Serum Institute of India Pvt. Ltd) for constant support and for providing the required analytical infrastructure. The authors are also thankful to Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune for the physical infrastructure and Department of Science and Technology and Engineering Research Board (DST-SERB), Govt. of India, New Delhi (File Number: YSS/2015/002035) for providing an optimized Supercomputer for docking and dynamics calculations. Mr. Kiran Bharat Lokhande acknowledges the ICMR (Indian Council of Medical Research), New Delhi, India for Senior Research Fellowship (Project ID: 2019-3458; file: ISRM/11(54)/2019).

Disclosure statement

The authors declare that there is no competing interest for the work carried out as mentioned in the manuscript.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.