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.

Aim. To select new tubulin-targeted inhibitors of plant fungal pathogens based on results of high-throughput virtual screening in Grid. Methods. Protein and ligand spatial structure modelling (I-Tasser, Grid), design and virtual screening ligands library (UCSF Dock 6, Grid), molecular docking (CCDC Gold), molecular dynamics simulation (Gromacs, Grid). Results. 240 structural models of tubulin molecules (82 α-, 111 β- and 47 γ-tubulin) from 62 species of phytopathogenic fungi were constructed. It was found that imidazole ligands, demonstrate strongest affinity to α- and β-tubulin. It was found that among α-, β- and γ-tubulin, taxol binding site of β-tubulin possess the strongest potential as the fungicidal drugs target. It was selected 50 leader compounds: 23 with affinity for GTP/GDF-exchange site and 27 with affinity for taxol-binding site. Conclusions. It was found, that in phytopathogenic fungi, taxol binding site of β-tubulin are the main fungicid drug target (in compare to other tubulin site or isotype). The highest affinity was predicted for the compounds F0478-0219, F0478-0166 and β-tubulin from Puccinia graminis f. sp. Tritici, as well as for the compound F0478-0385 and β-tubulin from Magnaporthe oryzae. Keywords: pathogenic fungi, fungicides, tubulin, virtual screening, Grid.

Aim. To determine the features of the ligand-protein interaction of glaziovianin A and human α-, β- and γ-tubulin. Methods. Protein and ligand spatial structure modelling (I-Tasser, Grid), molecular docking (CCDC Gold), molecular dynamics simulation (GROMACS). Results. Using the method of molecular docking in CCDC Gold ligand-protein complexes of glaziovianin A and human α-, β- and γ-tubulin were reconstructed. Studied ligand interactions in GTP/GDP-exchange and colchicine binding sites of different tubulin isotypes. The built ligand-protein complexes were studied using molecular dynamics simulations. Conclusions. Binding of glaziovianin A with human tubulin was confirmed exposing its derivatives as perspective tubulin effectors. The binding energies of ligand-protein interaction confirm higher affinity for β-tubulin molecules, and it was suggested that glazovianin A binding may occur at two alternative sites: GTP/GDP-exchange site and site of colchicine binding. Keywords: tubulin, glaziovianin A, binding, antitumor activity.