Hidden allosteric sites, as a novel type of allosteric site, are invisible in ligand-unbound (apo) crystal structures, but can emerge in ligand-bound (holo) crystal structures when a specific ligand binds to, and stabilizes, a unique conformation favored by the ligand. However, the identification of these sites is a significant challenge. Several computational and experimental approaches have been developed to identify such sites in proteins. Here, we outline these approaches, with a focus on examples of the successful use of such techniques. The discovery of hidden allosteric sites offers a new avenue for facilitating drug design by greatly expanding the repertoire of available drug targets, contributing to the search for allosteric drugs for the treatment of human diseases.

隐藏的变构位点是一种新型的变构位点，在配体未结合的（apo）晶体结构中不可见，但是当特定的配体结合并稳定了一个受青睐的独特构象时，可能会在配体结合的（holo）晶体结构中出现。通过配体。然而，识别这些位点是一个巨大的挑战。已经开发了几种计算和实验方法来鉴定蛋白质中的此类位点。在这里，我们概述了这些方法，并重点介绍了成功使用此类技术的示例。隐藏的变构位点的发现通过大大扩展可用药物靶标的种类，为便利药物设计提供了新途径，有助于寻找用于治疗人类疾病的变构药物。