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

J Biomol Struct Dyn. 2011 Feb;28(4):455-69. doi: 10.1080/07391102.2011.10508588.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anthrax / drug therapy*
  • Bacillus anthracis / chemistry*
  • Bacillus anthracis / drug effects
  • Bacillus anthracis / enzymology*
  • Catalytic Domain
  • Drug Design*
  • Humans
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Molecular Structure
  • N-Glycosyl Hydrolases / antagonists & inhibitors*
  • N-Glycosyl Hydrolases / chemistry*
  • Protein Structure, Tertiary
  • Protozoan Proteins / antagonists & inhibitors
  • Protozoan Proteins / chemistry
  • Pyrrolidines / chemistry*
  • Sequence Alignment
  • Trypanosoma vivax / enzymology

Substances

  • Protozoan Proteins
  • Pyrrolidines
  • N-Glycosyl Hydrolases
  • pyrrolidine