Abstract
Brugia malayi is a filarial nematode, which causes lymphatic filariasis in humans. In 1995, the disease has been identified by the World Health Organization (WHO) as one of the second leading causes of permanent and long-term disability and thus it is targeted for elimination by year 2020. Therefore, accurate filariasis diagnosis is important for management and elimination programs. A recombinant antigen (BmR1) from the Bm17DIII gene product was used for antibody-based filariasis diagnosis in “Brugia Rapid”. However, the structure and dynamics of BmR1 protein is yet to be elucidated. Here we study the three dimensional structure and dynamics of BmR1 protein using comparative modeling, threading and ab initio protein structure prediction. The best predicted structure obtained via an ab initio method (Rosetta) was further refined and minimized. A total of 5 ns molecular dynamics simulation were performed to investigate the packing of the protein. Here we also identified three epitopes as potential antibody binding sites from the molecular dynamics average structure. The structure and epitopes obtained from this study can be used to design a binder specific against BmR1, thus aiding future development of antigen-based filariasis diagnostics to complement the current diagnostics.
Highlights
Lymphatic filariasis has infected 120 million people worldwide especially in developing and under-developed countries and approximately 1.3 billion people in 81 countries are at risk of infection
InterProScan, SMART and Proteins Families database (Pfam) results have showed that the residue from 45–148 is a domain of unknown function 148 (DUF148)
Bm17DIII gene product of B. malayi in this study is the BmR1 protein with 206 amino acids
Summary
Lymphatic filariasis (commonly known as elephantiasis) has infected 120 million people worldwide especially in developing and under-developed countries and approximately 1.3 billion people in 81 countries are at risk of infection. One of the causative agents of lymphatic filariasis, falls under the category of nematodes that infects human and animals. Program for Elimination of Lymphatic Filariasis (GPELF) with two main strategies: to stop the spread of infection (interrupting transmission) and to alleviate the suffering of the affected population (controlling morbidity) [1]. One of the available diagnostics is the rapid immunochromatography detection of IgG4 antibody (Brugia Rapid). It is based on the recombinant antigen (BmR1) expressed from Bm17DIII gene (GenBank: AF225296) [2,3,4].
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