Flexibility vs Preorganization: Direct Comparison of Binding Kinetics for a Disordered Peptide and Its Exact Preorganized Analogues.

ABSTRACT: Many intrinsically disordered proteins, which are prevalent in nature, fold only upon binding their structured partner proteins. Such proteins have been hypothesized to have a kinetic advantage over their folded, preorganized analogues in binding their partner proteins. Here we determined the effects of ligand preorganization on the k_on for a biomedically important system: an intrinsically disordered p53 peptide ligand and the MDM2 protein receptor. Based on direct simulations of binding pathways, computed k_on values for fully disordered and preorganized p53 peptide analogues were within error of each other, indicating little if any kinetic advantage to being disordered or preorganized for binding the MDM2 protein. We also examined the effects of increasing the concen

SUBMITTER: Saglam AS 

PROVIDER: S-EPMC5903555 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature