Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.
Future Med Chem. 2011 Oct;3(14):1809-20. doi: 10.4155/fmc.11.128.
Surface plasmon resonance (SPR) offers a method of biophysical fragment screening that is fast, efficient, cost effective and accurate. SPR is increasingly being adopted as a secondary assay to validate fragment hits. Recently, technical advances have resulted in the emergence of SPR as a primary screening methodology for fragment-based drug discovery. Moreover, SPR biosensor assays can be developed for a wide range of proteins, including membrane proteins, such as G-protein-coupled receptors. In this review, we discuss the advantages and limitations of SPR fragment screening including experimental consideration of reducing false positive and false negative rates to a minimum. We discuss how ligand efficiency can be used both as a method to eliminate false positives and to understand which fragments in a library may be a source of false negatives.
表面等离子体共振（SPR）提供了一种快速、高效、经济且准确的生物物理片段筛选方法。SPR 越来越多地被用作验证片段命中的辅助测定方法。最近，技术的进步使得 SPR 成为基于片段的药物发现的主要筛选方法。此外，SPR 生物传感器测定法可用于开发广泛的蛋白质，包括膜蛋白，如 G 蛋白偶联受体。在这篇综述中，我们讨论了 SPR 片段筛选的优点和局限性，包括实验方面考虑将假阳性和假阴性率降至最低。我们讨论了如何使用配体效率来消除假阳性并了解库中的哪些片段可能是假阴性的来源。
