Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Curr Top Med Chem. 2013;13(1):64-77. doi: 10.2174/1568026611313010007.
Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most intra-protein conformational changes may be dynamically transmitted across protein-protein interaction and signaling networks of the cell. Allo-network drugs influence the pharmacological target protein indirectly using specific inter-protein network pathways. We show that allo-network drugs may have a higher efficiency to change the networks of human cells than those of other organisms, and can be designed to have specific effects on cells in a diseased state. Finally, we summarize possible methods to identify allo-network drug targets and sites, which may develop to a promising new area of systems-based drug design.
变构药物通常比针对同一蛋白质的变构药物更具特异性，副作用更少。在这里，我们从网络的角度概述了目前关于变构信号传递的知识，并表明大多数蛋白质内构象变化可能在细胞的蛋白质-蛋白质相互作用和信号网络中动态传递。变构网络药物使用特定的蛋白质间网络途径间接影响药理靶标蛋白。我们表明，变构网络药物可能比其他生物体更有效地改变人类细胞的网络，并且可以设计用于对患病状态的细胞产生特定的作用。最后，我们总结了识别变构网络药物靶点和作用位点的可能方法，这可能发展成为基于系统的药物设计的一个有前途的新领域。
