Simulation technique to design the antibiotics of the future

Simulation technique to design the antibiotics of the future

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Professor Adrian Mulholland et al., from the University of Bristol used computer simulations to reveal how bacteria are able to destroy antibiotics – a breakthrough which will help develop drugs that can effectively tackle infections in the future. They focused on the role of enzymes in the bacteria, which split the structure of the antibiotic and stops it from working, making the bacteria resistant. The findings published in the journal Chemical Communications, will help scientists to choose the best medicines for specific outbreaks and develop new antibiotics with a much lower risk of resistance.

The researchers used a special Nobel Prize-winning technique called QM/MM – quantum mechanics/molecular mechanics simulations- to learn how enzymes called ‘beta-lactamases’ react to antibiotics. The computer simulations revealed that the most important stage in the process is
when the enzyme ‘spits out’ the broken down antibiotic. If this happens quickly, then the enzyme is able to go on chewing up antibiotics. If it happens slowly, then the enzyme gets ‘clogged up’ and can’t break down any more antibiotics, meaning that the bacterium is more likely to die. The rate of this ‘spitting out’ depends on the height of the energy barrier for the reaction – if the barrier is high, it happens slowly; if it’s low, it happens much more quickly.