Design, structure prediction and molecular dynamics simulation of a fusion construct containing malaria pre-erythrocytic vaccine candidate, PfCelTOS, and human interleukin 2 as adjuvant

BMC Bioinformatics

Research Article

Shabnam Shamriz¹  Hamideh Ofoghi¹ 

[1] Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran, Iran;

关键词: Malaria;    Fusion protein;    Molecular modeling;    Molecular dynamics simulations;   

DOI  :  10.1186/s12859-016-0918-8

 received in 2015-10-06, accepted in 2016-01-29,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMalaria infection is still widespread in some parts of the world and threatens the lives of millions of people every year. Vaccines, especially oral vaccines are considered to be effective in reducing the burden of malaria morbidity and mortality. By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. This study was aimed towards designing and computational analysis of a fusion protein consisting of Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS) fused to human interleukin-2 (IL-2) and M cell-specific peptide ligand (Co1), as a step toward developing a vaccine candidate.ResultsTo our best knowledge, the three dimensional (3D) structure of CelTOS is not reported in protein database. Therefore, we carried out computational modeling and simulation in the hope of understanding the properties and structure of PfCelTOS. Then we fused IL-2 to PfCelTOS by a flexible linker and did in silico analysis to confirm the proper folding of each domain in the designed fusion protein. In the last step, Co1 ligand was added to the confirmed fusion structure using a rigid linker and computational analysis was performed to evaluate the final fusion construct. One structure out of five predicted by I-TASSER for PfCelTOS and fusion constructs was selected based on the highest value for C-score. Molecular dynamics (MD) simulation analysis indicated that predicted structures are stable during the simulation. Ramchandran Plot analysis of PfCelTOS and fusion constructs before and after MD simulation also represented that most residues were fallen in favorable regions.ConclusionIn silico study showed that Co1-(AEEEK)3- IL-2-(GGGGS)3-PfCelTOS construct has a constant structure and the selected linkers are effectively able to separate the domains. Therefore, data reported in this paper represents the first step toward developing of an oral vaccine candidate against malaria infection.

【 授权许可】

CC BY   
© Shamriz and Ofoghi. 2016