title: Theoretical study of Escherichia coli peptide deformylase inhibition by several drugs.
abstract: Because peptide deformylase (PDF) is essential for the initiation of translation in eubacteria but not in eukaryotes, it is a potentially interesting target for antibiotics. Computer simulation using docking software can be used to model protein-ligand interactions, and in this brief report we describe its use in optimizing the design in PDF-directed inhibitors. PDF was used as target for a set of five inhibitors with substantial structural differences. Docking results show that the compound 1BB2 (actinonin) binds with high affinity to the enzyme and produces the most stable complex, forming nine hydrogen bonds with the enzyme active site. Its binding energy is DeltaG = -31.880 kJ/mol. The modeling study shows that when the methyl group of 1BB2 is replaced with an amine group, the binding energy is increased to -35.316 kJ/mole. This enhancement is more marked (DeltaG = -41.141 kJ/mol) when the propyl group and the five-membered ring of 1BB2 are replaced by an amide group and a phenyl ring, respectively. We describe an attempt to design better antibiotics on the basis of a computer-aided simulation of the interaction between a drug and its target molecule.
authors.affiliation: Laboratory of Microbiological Engineering and Applications, Department of Biology Faculty of Sciences, Mentouri University, Constantine, Algeria. abchikhi@yahoo.fr
authors.forename: Abdelouahab
authors.initials: A
authors.lastname: Chikhi
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Bensegueni
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Boulahrouf
authors.forename: Mustapha
authors.initials: M
authors.lastname: Bencharif
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D003198:Computer Simulation; D017076:Computer-Aided Design; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology*; D008024:Ligands; D008958:Models, Molecular; D013816:Thermodynamics
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D008024:Ligands; D000581:Amidohydrolases; C084507:peptide deformylase