Emerging role of surface plasmon resonance in fragment-based drug discovery

Abstract

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.