Affiliations: Laboratory of Materials Chemistry, Department of
Chemistry, Faculty of Sciences, Mentouri University, Constantine, Algeria | Laboratory of Microbiological Engineering and
Applications, Department of Biology, Faculty of Sciences, Mentouri University,
Constantine, Algeria
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
ΔG=−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
(ΔG=−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.
