N-arylnaphthylamines as inhibitors of Human Immunodeficiency Virus Integrase - Lens Epithelium-Derived Growth Factor interactions: Theoretical studies.

Kapusta, Karina; Sizochenko, Natalia; Anderson, Micah L; Kolodziejczyk, Wojciech; Voronkov, Eugene O; Saloni, Julia; Leszczynski, Jerzy; Hill, Glake A

Presented work reports a comprehensive theoretical study on the inhibitory nature of N-arylnaphthylamines in Human Immunodeficiency Virus Integrase (HIV IN) - Lens Epithelium-Derived Growth Factor (LEDGF/p75) complexes. Factors influencing the inhibition efficiency in AlphaScreen% assay are evaluated and explained through the structure- and ligand-based studies; including molecular docking, molecular dynamics calculations, and quantitative structure-activity relationship (QSAR) approach. It has been shown that N-arylnaphthylamines possess a wide variety of binding poses. Three QSAR models have been developed using structural descriptors and descriptors derived from docking calculations. The activity of untested N-arylnaphthylamines have been predicted using the most successful model. Proposed here technique could become a useful tool for ligand selection, accelerating the development of a new generation of anti-HIV medications.