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A method for estimation of immunogenic determinants mutability: case studies of HIV1 gp120 and diphtheria toxin

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Author(s): Khrustalev Vladislav Victorovich | Barkovsky Eugene Victorovich | Vasilevskaya Alla Evgenyevna | Skripko Svetlana Michailovna | Kolodkina Valentina Leonidovna | Ignatyev Georgiy Michailovich | Semizon Pavel Anatolyevich

Journal: Journal of Integrated OMICS
ISSN 2182-0287

Volume: 1;
Issue: 2;
Start page: 236;
Date: 2011;
Original page

Keywords: Mutational pressure | Sequence analysis | B-cell epitopes | HIV1 vaccine | gp120 | Diphtheria toxin

ABSTRACT
There is a need for the method which helps to choose the less mutable immunogenic determinant for the design of recombinant or synthetic vaccines and ELISA test-systems. Our method based on the directional mutational pressure theory includes two steps: estimation of symmetric and asymmetric mutational pressure directions in a gene coding for a protein of interest; and selection of regions coding for its immunogenic determinants which are less prone to missense mutation occurrence and so, to immune escaping. Three original computer algorithms (“VVK Sliding Window”, “VVK VarInvar” and “VVK Protective Buffer” available via www.barkovsky.hotmail.ru) have been created to perform all the necessary calculations and tests. “VVK Sliding Window” calculates nucleotide usage in fourfold and twofold degenerated sites, as well as usage of missense, nonsense and synonymous sites for each kind of nucleotide mutation along the length of a coding region, while “VVK Protective Buffer” calculates those indexes in a set of sequences. “VVK VarInvar” calculates percentage of variable sites in a set of aligned sequences, as well as nucleotide usage in invariable sites. Our method has been tested on HIV1 gp120 protein and on diphtheria toxin. The less mutable epitopes have been found for both proteins. Finally, it has been shown that antibodies recognizing the less mutable epitope of gp120 can be found in 80.22% of HIV1-infected persons.
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