Khor Bee Yin, Tye Gee Jun, Lim Theam Soon, Noordin Rahmah, Choong Yee Siew
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia.
Int J Mol Sci. 2014 Jun 19;15(6):11082-99. doi: 10.3390/ijms150611082.
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.
马来布鲁线虫是一种丝虫线虫，可导致人类淋巴丝虫病。1995年，该疾病被世界卫生组织（WHO）确定为导致永久性和长期残疾的第二大主要原因之一，因此计划到2020年消除该疾病。所以，准确的丝虫病诊断对于管理和消除计划至关重要。来自Bm17DIII基因产物的重组抗原（BmR1）被用于“布鲁氏快速检测法”中基于抗体的丝虫病诊断。然而，BmR1蛋白的结构和动力学尚未阐明。在此，我们使用比较建模、穿线法和从头算蛋白质结构预测来研究BmR1蛋白的三维结构和动力学。通过从头算方法（Rosetta）获得的最佳预测结构进一步进行了优化和最小化处理。总共进行了5纳秒的分子动力学模拟以研究该蛋白质的堆积情况。在此，我们还从分子动力学平均结构中确定了三个表位作为潜在的抗体结合位点。本研究获得的结构和表位可用于设计针对BmR1的结合物，从而有助于基于抗原的丝虫病诊断方法的未来发展，以补充当前的诊断方法。
