Theoretical Studies of Bacterial Ribosome Antagonists

我们建议对氨基糖苷类抗生素与30S核糖体亚基的相互作用进行计算研究。这些化合物是细菌翻译的抑制剂，是已知的最古老的抗生素之一。由于它们的年龄和广泛使用，它们受到越来越多的细菌耐药性的影响。此外，尽管它们专门针对细菌核糖体，但它们也对真核核糖体起到较小程度的作用，导致对人类的毒性。最近解决的细菌30S核糖体的原子分辨结构，既是自由的，也是与三种氨基糖苷类抗生素络合的，为我们提供了一个前所未有的机会来设计尚未出现细菌耐药性因素的新药，这些新药对患者来说没有那么大的毒性。

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.