英国发现抗生素耐药菌株的新机制

 
研究人员通过大规模计算机仿真研究的结果，发现一个分子结构的微小改变，可以说明肺炎链球菌产生耐药性的原因。这种细菌每年导致大量儿童肺炎并夺去3.5百万人的生命，主要是在发展中国家。

迄今为止，还没有进行过实验研究分子水平的改变是如何导致这种药物耐药性的。这些新发现的结果对设计研制新的能够有效对抗这种耐药菌株的药物十分重要。这些结果是由Peter教授和来自玛丽女王伦敦大学研究院、伦敦大学的研究人员，通过使用计算机模型技术二发现的。他们的研究结果发表在2005年8月15日的《皇家学会的哲学学报》的专刊之上。

研究人员使用从来自其它细菌的实验资料构建了这些位点的计算机模型，在这些位点药物分子与细菌的蛋白质分子相互作用。然后他们进行模拟并观察当药物分子进入正常和耐药肺炎链球菌的这些位点后，到底发生了什么。这种模拟仿真与可视化探索了大量的平行密码，在英国国家超级计算机部门运行。

Coveny教授与他的同事发现了正常与耐药菌株之间很小但是很敏感的结构差异，而正是这些差异导致了药物耐药性的产生。在正常菌株，药物分子能够与该位点紧密结合，但是在耐药菌株，药物进入此位点然后慢慢的漂移。研究人员相信这个发现指出了研制新药战胜这种疾病的途径。
 
New Insights Into Antibiotic Resistance
 
Researchers working with large-scale computer simulations have discovered a tiny change in molecular structure that may account for drug resistance in Streptomices pneumoniae, the organism that causes childhood pneumonia and claims 3.5 million lives a year, mainly in developing countries.

Until now, no experiments have been conducted to find how changes at the molecular level are causing this resistance. The new finding may be very useful in designing new drugs that are effective against the drug-resistant strain. It was discovered by Prof. Peter Coveny and co-workers from the University College London (UK) and Queen Mary, University of London (UK), using computer modeling techniques. The results of their work were published in the August 15, 2005, issue of a special theme issue of Philosophical Transactions of the Royal Society.

The researchers took experimental data gathered from other organisms to build computer models of the sites where drug molecules interact with an organism’s protein molecules. Then they ran simulations and visualized what happens when a drug molecule approaches each site for both normal and drug-resistant strains of S pneumoniae. The simulations and visualizations exploited highly scalable parallel code, running on the UK’s national supercomputing facilities.

Prof. Coveny and his colleagues could see that a very small but subtle difference in structure beween the normal and drug-resistant strains was to blame for the drug resistance. In the normal strain, a drug molecule binds tightly to the site, but in the drug-resistant strain, it approaches and then drifts slowly away. The researchers believe this finding may point the way to new drugs that can combat disease.