Mapping the energy landscape of protein-ligand binding via linear free energy relationships determined by protein NMR relaxation dispersion.

ABSTRACT: Biochemical signaling is mediated by complexes between macromolecular receptors and their ligands, with the duration of the signal being directly related to the lifetime of the ligand-receptor complex. In the field of drug design, the recognition that drug efficacy in vivo depends on the lifetime of the drug-protein complex has spawned the concept of designing drugs with particular binding kinetics. To advance this field it is critical to investigate how the molecular details of designed ligands might affect the binding kinetics, as well as the equilibrium binding constant. Here we use protein NMR relaxation dispersion to determine linear free energy relationships involving the on- and off-rates and the affinity for a series of congeneric ligands targeting the carbohydrate recogniti

SUBMITTER: Stenstrom O 

PROVIDER: S-EPMC8341105 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature