Protein Dynamics in Drug Combinations: a Linear Superposition of Individual-Drug Responses
Protein Dynamics in Drug Combinations: a Linear Superposition of Individual-Drug Responses
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DOI：
10.1016/j.cell.2010.02.011
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发表时间：
2010-03-05
期刊：
影响因子：
64.5
通讯作者：
Alon, Uri
中科院分区：
文献类型：
--
作者：
Geva-Zatorsky, Naama;Dekel, Erez;Alon, Uri
药物和药物组合对细胞和生物体具有复杂的生物学效应。关于药物如何影响决定这些效应的蛋白质动力学，人们知之甚少。在这里，我们使用动态蛋白质组学方法来准确地跟踪人体细胞中对13种不同药物反应的15种蛋白质水平。我们发现，蛋白质动力学响应药物的组合准确地描述了他们对个别药物的反应的线性叠加（加权和）。该叠加中的权重描述了每种药物对每种蛋白质的相对影响。使用这些权重，我们表明，一个可以预测的动态在一个三种药物或四种药物组合的基础上的药物对的动态。我们的方法可能消除了随着药物数量呈指数级增加实验数量的需要，并表明有可能合理地控制特定药物组合的蛋白质动力学。
Drugs and drug combinations have complex biological effects on cells and organisms. Little is known about how drugs affect protein dynamics that determine these effects. Here, we use a dynamic proteomics approach to accurately follow 15 protein levels in human cells in response to 13 different drugs. We find that protein dynamics in response to combinations of drugs are described accurately by a linear superposition ( weighted sum) of their response to individual drugs. The weights in this superposition describe the relative impact of each drug on each protein. Using these weights, we show that one can predict the dynamics in a three-drug or four-drug combination on the basis of the dynamics in drug pairs. Our approach might eliminate the need to increase the number of experiments exponentially with the number of drugs and suggests that it might be possible to rationally control protein dynamics with specific drug combinations.