Kinetic binding assays for the analysis of protein-ligand interactions.
Kinetic binding assays for the analysis of protein-ligand interactions.
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DOI：
10.1016/j.ddtec.2015.08.004
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发表时间：
2015-10-01
期刊：
影响因子：
--
通讯作者：
Meyer-Almes, Franz-Josef
中科院分区：
文献类型：
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作者：
Meyer-Almes, Franz-Josef
在过去几年中，结合动力学在药物发现中的停留时间和结合速率的重要性已被广泛接受。此外，越来越多的证据表明，药物与其靶分子的最佳结合机制与生理功效和选择性以及药物安全性有关。基于均相荧光的结合测定已被证明能够实现仅需要少量蛋白质的高通量动力学，并且可以开发用于阐明甚至复杂的分子识别机制。提出了一种通用方法，在综合全局拟合分析中结合高质量的动力学和平衡数据，产生最可能的结合机制。
The importance of binding kinetics in terms of residence time and on-rate in drug discovery has been broadly accepted in the past few years. Furthermore, evidence has accumulated that the optimal binding mechanism of a drug to its target molecule is related to physiological efficacy as well as selectivity and thus drug safety. Homogeneous fluorescence-based binding assays have been shown to enable high throughput kinetics requiring only small amounts of protein and can be developed to elucidate even complex mechanisms of molecular recognition. A generalized approach is proposed that combines high quality kinetic and equilibrium data in an Integrated Global Fit analysis yielding the most probable binding mechanism.