Exploring the Binding Mechanism of a Supramolecular Tweezer CLR01 to 14-3-3σ Protein via Well-Tempered Metadynamics.

ABSTRACT: Using supramolecules for protein function regulation is an effective strategy in chemical biology and drug discovery. However, due to the presence of multiple binding sites on protein surfaces, protein function regulation via selective binding of supramolecules is challenging. Recently, the functions of 14-3-3 proteins, which play an important role in regulating intracellular signaling pathways via protein-protein interactions, have been modulated using a supramolecular tweezer, CLR01. However, the binding mechanisms of the tweezer molecule to 14-3-3 proteins are still unclear, which has hindered the development of novel supramolecules targeting the 14-3-3 proteins. Herein, the binding mechanisms of the tweezer to the lysine residues on 14-3-3σ (an isoform in 14-3-3 protein f

SUBMITTER: Zhou X 

PROVIDER: S-EPMC9133541 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature