We propose a computational investigation of the interaction of aminoglycoside antibiotics with the 30S ribosomal subunit. These compounds are inhibitors of bacterial translation, and are among the oldest known antibiotics. As a consequence of their age and wide use, they are subject to an increasing array of bacterial resistance. In addition, although they specifically target the bacterial ribosome, they also act to a lesser extent against the eukaryotic ribosome, resulting in human toxicity. The recently solved atomic resolution structure of the bacterial 30S ribosome, both free and complexed with three aminoglycoside antibiotics, provides us with an unprecedented opportunity to design new drugs for which bacterial resistance factors have not yet arisen, and which are not as toxic to patients.
| Greenbaum, Doron C; Arnold, William D; Lu, Felice et al. (2002) Small molecule affinity fingerprinting. A tool for enzyme family subclassification, target identification, and inhibitor design. Chem Biol 9:1085-94 |
