研究人員通過大規(guī)模計(jì)算機(jī)仿真研究的結(jié)果，發(fā)現(xiàn)一個(gè)分子結(jié)構(gòu)的微小改變，可以說明肺炎鏈球菌產(chǎn)生耐藥性的原因。這種細(xì)菌每年導(dǎo)致大量兒童肺炎并奪去3.5百萬人的生命，主要是在發(fā)展中國家。

迄今為止，還沒有進(jìn)行過實(shí)驗(yàn)研究分子水平的改變是如何導(dǎo)致這種藥物耐藥性的。這些新發(fā)現(xiàn)的結(jié)果對設(shè)計(jì)研制新的能夠有效對抗這種耐藥菌株的藥物十分重要。這些結(jié)果是由Peter教授和來自瑪麗女王倫敦大學(xué)研究院、倫敦大學(xué)的研究人員，通過使用計(jì)算機(jī)模型技術(shù)二發(fā)現(xiàn)的。他們的研究結(jié)果發(fā)表在2005年8月15日的《皇家學(xué)會的哲學(xué)學(xué)報(bào)》的專刊之上。

研究人員使用從來自其它細(xì)菌的實(shí)驗(yàn)資料構(gòu)建了這些位點(diǎn)的計(jì)算機(jī)模型，在這些位點(diǎn)藥物分子與細(xì)菌的蛋白質(zhì)分子相互作用。然后他們進(jìn)行模擬并觀察當(dāng)藥物分子進(jìn)入正常和耐藥肺炎鏈球菌的這些位點(diǎn)后，到底發(fā)生了什么。這種模擬仿真與可視化探索了大量的平行密碼，在英國國家超級計(jì)算機(jī)部門運(yùn)行。

Coveny教授與他的同事發(fā)現(xiàn)了正常與耐藥菌株之間很小但是很敏感的結(jié)構(gòu)差異，而正是這些差異導(dǎo)致了藥物耐藥性的產(chǎn)生。在正常菌株，藥物分子能夠與該位點(diǎn)緊密結(jié)合，但是在耐藥菌株，藥物進(jìn)入此位點(diǎn)然后慢慢的漂移。研究人員相信這個(gè)發(fā)現(xiàn)指出了研制新藥戰(zhàn)勝這種疾病的途徑。
 
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.