title: The structure and dynamics of BmR1 protein from Brugia malayi: in silico approaches.
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.
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia. kbyin89@gmail.com.
authors.forename: Bee Yin
authors.initials: BY
authors.lastname: Khor
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia. geejun@usm.my.
authors.forename: Gee Jun
authors.initials: GJ
authors.lastname: Tye
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia. theamsoon@usm.my.
authors.forename: Theam Soon
authors.initials: TS
authors.lastname: Lim
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia. rahmah8485@gmail.com.
authors.forename: Rahmah
authors.initials: R
authors.lastname: Noordin
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia. yeesiew@usm.my.
authors.forename: Yee Siew
authors.initials: YS
authors.lastname: Choong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017178:Brugia malayi / Q000378:metabolism*; D004605:Elephantiasis, Filarial / Q000469:parasitology; D015801:Helminth Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D015801:Helminth Proteins