NDLI: De novo design of immunoreactive conformation-specific HIV-1 epitopes based on Top7 scaffold

Content Provider	Royal Society of Chemistry (RSC)
Author	Dhalia, Rafael Soares, Thereza A. Krieger, Marco A. Marques, Ernesto T. A. Viana, Isabelle F. T. Lima, Lucianna F. O. Lins, Roberto D.
Copyright Year	2013
Abstract	Epitope exposure strategies often fail due to high conformational instability, resulting in loss of native conformation and fast degradation. Protein scaffolding, where a structural element of an antigen protein is transplanted into a scaffold acceptor protein, has been employed as an alternative solution. However, while this approach aims to preserve the epitope structure, it frequently results in unstable chimeric scaffolds. To overcome this issue, we employed a novel computational approach to rationally engineer conformational antigens into a highly stable scaffold protein. This strategy is showcased to display conformational HIV-1 gp41-based epitopes in their native structure. From HIV-1 antigen sequence databases, we have identified short sequences with the most probable antibody-recognizable regions. These sequences were inserted into or replaced regions of the original Top7 protein with analogous secondary structure assignment. Molecular dynamics simulations were used to characterize the protein stability and structural dynamic of the chimeric proteins, leading to a selection of promising candidates whose immunogenic epitopes are suitably exposed for antibody recognition. These computer-designed recombinant proteins were produced in bacteria using codon optimized DNA sequences and their diagnostic performance was assessed by liquid microarray against a human cohort of 47 sera samples. Our results show that the Top7 protein is a suitable scaffold to provide the required structural stability to predetermined target shapes and sequences, allowing the potential use of the chimeric proteins as antigens for specific antibody recognition and/or stimulation of immune response.
Starting Page	11790
Ending Page	11800
Page Count	11
File Format	HTM / HTML PDF
ISSN	20462069
Volume Number	3
Issue Number	29
Journal	RSC Advances
DOI	10.1039/c3ra41562g
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Epitope Top7 Gp41 Molecular dynamics Bacteriophage Microarray Biomolecular structure Protein Antigen Genetic code Subtypes of HIV DNA Scaffold protein
Content Type	Text
Resource Type	Article
Subject	Chemistry Chemical Engineering

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