Bijvoet Center for Biomolecular Research, Science Faculty - Chemistry, Utrecht University, 3584CH Utrecht, The Netherlands.
Curr Opin Struct Biol. 2013 Dec;23(6):868-77. doi: 10.1016/j.sbi.2013.07.001. Epub 2013 Jul 19.
Connecting three dimensional structure and affinity is analogous to seeking the 'Archimedean point', a vantage point from where any observer can quantitatively perceive the subject of inquiry. Here we review current knowledge and challenges that lie ahead of us in the quest for this Archimedean point. We argue that current models are limited in reproducing measured data because molecular description of binding affinity must expand beyond the interfacial contribution and also incorporate effects stemming from conformational changes/dynamics and long-range interactions. Fortunately, explicit modeling of various kinetic schemes underlying biomolecular recognition and confined systems that reflect in vivo interactions are coming within reach. This quest will hopefully lead to an accurate biophysical interpretation of binding affinity that would allow unprecedented understanding of the molecular basis of life through unraveling the why's of interaction networks.
连接三维结构和亲和力类似于寻找“阿基米德点”，从这个有利位置，任何观察者都可以定量地感知探究的对象。在这里，我们回顾了当前的知识和挑战，以及我们在追求这个阿基米德点的过程中所面临的挑战。我们认为，目前的模型在再现测量数据方面存在局限性，因为结合亲和力的分子描述必须不仅仅局限于界面贡献，还必须纳入源自构象变化/动力学和远程相互作用的影响。幸运的是，正在实现对生物分子识别和反映体内相互作用的受限系统的各种动力学方案的明确建模。这一探索有望对结合亲和力进行准确的生物物理解释，从而通过揭示相互作用网络的“为什么”，对生命的分子基础有前所未有的理解。
