1D and 2D NMR for KRAS:Ligand Binding

Abstract

Fragment-based screening by ligand-observed 1D NMR and binding interface mapping by protein-observed 2D NMR are popular methods used in drug discovery. These methods allow researchers to detect compound binding over a wide range of affinities and offer a simultaneous assessment of solubility, purity, and chemical formula accuracy of the target compounds and the ¹⁵N-labeled protein when examined by 1D and 2D NMR, respectively. These methods can be applied for screening fragment binding to the active (GMPPNP-bound) and inactive (GDP-bound) states of oncogenic KRAS mutants.

Keywords: CSP; FBDD; FBS; HSQC titration; KRAS; NMR screening; STD; WaterLOGSY.