Kinetic versus thermodynamic control of mutational effects on protein homeostasis: A perspective from computational modeling and experiment.

ABSTRACT: The effect of mutations in individual proteins on protein homeostasis, or "proteostasis," can in principle depend on the mutations' effects on the thermodynamics or kinetics of folding, or both. Here, we explore this issue using a computational model of in vivo protein folding that we call FoldEcoSlim. Our model predicts that kinetic versus thermodynamic control of mutational effects on proteostasis hinges on the relationship between how fast a protein's folding reaction reaches equilibrium and a critical time scale that characterizes the lifetime of a protein in its environment: for rapidly dividing bacteria, this time scale is that of cell division; for proteins that are produced in heterologous expression systems, this time scale is the amount of time before the protein is harvested; fo

SUBMITTER: Pobre KFR 

PROVIDER: S-EPMC6566562 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature