Open AccessStructure-based virtual screening for new lead compounds targeted Plasmodium α-tubulin
Author(s) -
O. V. Rayevsky,
O. M. Demchyk,
П. А. Карпов,
S. P. Ozheredov,
S. I. Spivak,
А. І. Yemets,
Ya. B. Blume
Publication year - 2021
Publication title -
faktori eksperimentalʹnoï evolûcìï organìzmìv
Language(s) - English
Resource type - Journals
eISSN - 2415-3826
pISSN - 2219-3782
DOI - 10.7124/feeo.v28.1389
Subject(s) - pharmacophore , virtual screening , plasmodium falciparum , docking (animal) , computational biology , ligand (biochemistry) , tubulin , chemistry , combinatorial chemistry , biology , malaria , biochemistry , microbiology and biotechnology , microtubule , receptor , medicine , nursing , immunology
Aim. Search for new dinitroaniline and phosphorothioamide compounds, capable of selective binding with Plasmodium α-tubulin, affecting its mitotic apparatus. Methods. Structural biology methods of computational prediction of protein-ligand interaction: molecular docking, molecular dynamics and pharmacophore analysis. Selection of compounds based on pharmacophore characteristics and virtual screening results. Results. The protocol and required structural conditions for target (α-tubulin of P. falciparum) preparation and correct modeling of the ligand-protein interaction (docking and virtual screening) were developed. The generalized pharmacophore model of ligand-protein interaction and key functional groups of ligands responsible for specific binding were identified. Conclusions. Based on results of virtual screening, 22 commercial compounds were selected. Identified compounds proposed as potential inhibitors of Plasmodium mitotic machinery and the base of new antimalarial drugs.
Keywords: malaria, Plasmodium, intermolecular interaction, dinitroaniline derived, phosphorothioamidate derived.