Franklin T J
J Neural Transm Suppl. 1983;18:55-60.
The primary events in the biological signals elicited by hormonal ligands are the initial binding of the ligands to their receptors and the consequent changes in the receptors that this induces. Although the effects of chemical modifications of ligands on their affinity for receptors have been intensively studied in several systems, the influence of such changes upon the ability of ligands to induce the conformational changes in receptors that are necessary for the expression of agonism has been largely ignored. This paper considers some theoretical and experimental approaches to the problem of the relationships between ligand structure, binding energy and the induction of conformational change in receptors. The significance of the concept of productive and non-productive ligand binding to proteins previously applied with considerable success by Jencks to the understanding of enzyme catalysis, is highlighted. Given a series of closely related ligands it is possible to estimate the energetic contributions of substituent groups not only to the binding affinity to the receptor but also to the induction of conformational change in the receptor provided that the rate of conformational change, can be monitored.
激素配体引发的生物信号中的主要事件是配体与其受体的初始结合以及由此诱导的受体的后续变化。尽管在多个系统中已对配体化学修饰对其与受体亲和力的影响进行了深入研究，但此类变化对配体诱导受体构象变化（这是激动作用表达所必需的）能力的影响在很大程度上被忽视了。本文考虑了一些理论和实验方法，以解决配体结构、结合能与受体构象变化诱导之间的关系问题。强调了富有成效和无成效的配体与蛋白质结合这一概念的重要性，Jencks此前曾相当成功地运用这一概念来理解酶催化作用。对于一系列密切相关的配体，只要能够监测构象变化的速率，就有可能不仅估计取代基对与受体结合亲和力的能量贡献，还能估计其对受体构象变化诱导的能量贡献。
