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|Title:||A combination of molecular dynamics and docking calculations to explore the binding mode of ADS-J1, a polyanionic compound endowed with anti-HIV-1 activity.||Authors:||Manetti, Fabrizio
ARMAND UGÓN, M
CLOTET CODINA, I
|Issue Date:||2006||Project:||None||Journal:||JOURNAL OF CHEMICAL INFORMATION AND MODELING||Abstract:||
The HIV-1 entry process is an important target for the design of new pharmaceuticals for the multidrug therapy of AIDS. A lot of polyanionic compounds, such as polysulfonated and polysulfated, are reported in the literature for their ability to block early stages of HIV-1 replication. Several studies have been performed to elucidate the mechanism of the anti-HIV-1 activity of sulfated polysaccharides and polyanions in general, including binding to cell surface CD4 and interfering with the gp120−coreceptor interaction. Here, we show molecular modeling investigations on ADS-J1, a polyanionic compound with anti-HIV activity that is able to interfere with gp120−coreceptor interactions. Agreeing with experimental data, computer simulations suggested that the V3 loop of gp120 was the preferential binding site for ADS-J1 onto HIV-1. Moreover, mutations induced by the inhibitor significantly changed the stereoelectronic properties of the gp120 surface, justifying a marked drop in the affinity of ADS-J1 toward an ADS-J1-resistant HIV-1 strain.
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