Analysis of the Dynamics of a Complex, Multipathway Reaction: Insulin Dimer Dissociation.

ABSTRACT: The protein hormone insulin forms a homodimer that must dissociate to bind to its receptor. Understanding the kinetics and mechanism of dissociation is essential for the rational design of therapeutic analogs. In addition to its physiological importance, this dissociation process serves as a paradigm for coupled (un)folding and (un)binding. Based on previous free energy simulations, insulin dissociation is thought to involve multiple pathways with comparable free energy barriers. Here, we analyze the mechanism of insulin dimer dissociation using a recently developed computational framework for estimating kinetic statistics from short-trajectory data. These statistics indicate that the likelihood of dissociation (the committor) closely tracks the decrease in the number of (native and nonnat

SUBMITTER: Jeong K 

PROVIDER: S-EPMC12768575 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature