Structure Prediction And Scfv Design For Bmr1 Antigen Of Brugia Malayi
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Date
2014-12
Authors
BEE YIN, KHOR
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Abstract
Lymphatic filariasis which is caused by one of the filarial nematode, Brugia malayi, has been identified by World Health Organization for elimination since year 1997. The recombinant antigen from B. malayi (BmR1) was found to be highly specific and sensitive in the antibody detection test against brugian filariasis (Brugia Rapid). Therefore, this antigen is an ideal candidate for the development of antigen detection test to complement the current Brugia Rapid. In this study, computational approach was implemented to obtain three-dimensional structure of BmR1 antigen, to study the functional domain, to predict the potential epitopes and to design single chain variable fragment (scFv) specific to BmR1. Predictive structures were obtained via comparative modelling, threading and ab initio approaches. Evaluation studies showed that the structure built by ab initio (Rosetta) was the most optimal compared to structures built by other methods. The further refined and optimized structure was shown to be stable and posses good quality throughout 5 ns of molecular dynamics simulations. Three potential epitopes (residues 37-49, 104-112 and 125-148) were predicted by linear and conformational epitopes prediction server. Specific scFv towards these epitopes were designed using two main methods: the generation of hot spot libraries and high shape complementarity conformations. A total of 200 scFv designs with binding energy (<-20 R.E.U) and shape complementarity (Sc>0.5) were obtained. Key residues that played crucial roles in enhancing the interactions with BmR1 antigen were also identified. These designed scFv were predicted to be highly specific towards the BmR1 antigen and may be useful for in vitro testing prior to the development of antigen detection test.
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Structure Prediction And Scfv Design , For Bmr1 Antigen Of Brugia Malayi