title: Design of new chemotherapeutics against the deadly anthrax disease. Docking and molecular dynamics studies of inhibitors containing pyrrolidine and riboamidrazone rings on nucleoside hydrolase from Bacillus anthracis.
abstract: Anthrax is a disease caused by Bacillus anthracis, a dangerous biological warfare agent already used for both military and terrorist purposes. An important selective target for chemotherapy against this disease is nucleoside hydrolase (NH), an enzyme still not found in mammals. Having this in mind we have performed molecular docking studies, aiming to analyze the three-dimensional positioning of six known inhibitors of Trypanosoma vivax NH (TvNH) in the active site of B. anthracis NH (BaNH). We also analyzed the main interactions of these compounds with the active site residues of BaNH and the relevant factors to biological activity. These results, together with further molecular dynamics (MD) simulations, pointed out to the most promising compounds as lead for the design of potential inhibitors of BaNH. Most of the docking and MD results obtained corroborated to each other. Additionally, the docking results also suggested a good correlation with experimental data.
authors.affiliation: Laboratory of Molecular Modeling Applied, Chemical and Biological Defense, Military Institute of Engineering, Praca General Tiburcio 80, 22290-270 Rio de Janeiro, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Guimarães
authors.forename: Aline A
authors.initials: AA
authors.lastname: Oliveira
authors.forename: Elaine F F
authors.initials: EF
authors.lastname: da Cunha
authors.forename: Teodorico C
authors.initials: TC
authors.lastname: Ramalho
authors.forename: Tanos C C
authors.initials: TC
authors.lastname: França
mesh_terms: D000595:Amino Acid Sequence; D000881:Anthrax / Q000188:drug therapy*; D001408:Bacillus anthracis / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology*; D020134:Catalytic Domain; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry*; D016415:Sequence Alignment; D016689:Trypanosoma vivax / Q000201:enzymology
chemical_list: D015800:Protozoan Proteins; D011759:Pyrrolidines; D009699:N-Glycosyl Hydrolases; C032519:pyrrolidine