Theoretical Investigations on Interactions Between Pharmacon Molecules and Receptor Models V: Construction of a Model for the Ribosomal Binding Site of Chloramphenicol

Interaction energies between the most stable conformations of chloramphenicol and Chloramphenicol derivatives and amino acids as binding site models were calculated using the multipol-bond-polarizability method. The resulting energies were correlated with the antibiotic activities of the drug molecules. A receptor model for the chloramphenicol molecule was constructed which consists of arginine and histidine as binding sites for the acyl sidechain and the substituted aromatic ring system, respectively. The significance of the hypothetical receptor was challenged by determination of low energy conformations of a fragment from the ribosomal chloramphenicol binding protein L16 which comprises the single histidine residue of this protein. The results of these ECEPP calculations and of experimental histidine blockade prove the receptor model to be realistic.