Theoretical Studies of Bacterial Ribosome Antagonists

我们提出了一个计算调查的相互作用的氨基糖苷类抗生素与30 S核糖体亚基。这些化合物是细菌翻译的抑制剂，是已知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，尽管它们特异性靶向细菌核糖体，但它们也在较小程度上对真核核糖体起作用，导致人类毒性。最近解决的细菌30S核糖体的原子分辨率结构，无论是游离的还是与三种氨基糖苷类抗生素复合的，都为我们提供了一个前所未有的机会来设计新的药物，这些药物的细菌耐药因素尚未出现，并且对患者没有毒性。

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.