Determination of the invariant structural elements for the third variable domain of the HIV-1 gp120 protein by molecular modeling

Yu. V. Kornoushenko ; I. V. Anishchenko ; A. V. Tuzikov ; A. M. Andrianov

Matematičeskaâ biologiâ i bioinformatika, Tome 6 (2011), pp. 298-311.

Résumé

Static and dynamic models for the 3D structure of the HIV-1 gp120 third variable domain (V3 loop) were built by computer modeling for the four differing in genetic and biological properties viral modifications that circulate in the countries of Eastern Europe, such as Russia, Belarus and Ukraine. Comparative analysis of the V3 calculated structures was carried out, allowing one to disclose a series of regularities in the spatial arrangement of this site of the HIV-1 envelope, which forms the principal target for neutralizing antibodies as well as the determinant responsible for penetration of the viral genome into macrophages and T-lymphocytes. As a result, despite the HIV-1 genetic diversity, the V3 loop was shown to form at least three conserved structural motifs including the gp120 residues critical for cell tropism. These invariant structural elements of the HIV-1 V3 loop are considered as the promising targets for the design of novel, potent and broad antiviral agents.

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