Second harmonic generation detection of Ras conformational changes and discovery of a small molecule binder.

ABSTRACT: Second harmonic generation (SHG) is an emergent biophysical method that sensitively measures real-time conformational change of biomolecules in the presence of biological ligands and small molecules. This study describes the successful implementation of SHG as a primary screening platform to identify fragment ligands to oncogenic Kirsten rat sarcoma (KRas). KRas is the most frequently mutated driver of pancreatic, colon, and lung cancers; however, there are few well-characterized small molecule ligands due to a lack of deep binding pockets. Using SHG, we identified a fragment binder to KRas^G12D and used ¹H ¹⁵N transverse relaxation optimized spectroscopy (TROSY) heteronuclear single-quantum coherence (HSQC) NMR to characterize its binding site as a pocket a

SUBMITTER: Donohue E 

PROVIDER: S-EPMC6717309 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature