Equilibrium Ensembles for Insulin Folding from Bias-Exchange Metadynamics.

ABSTRACT: Earliest events in the aggregation process, such as single molecule reconfiguration, are extremely important and the most difficult to characterize in experiments. To this end, we have used well-tempered bias exchange metadynamics simulations to determine the equilibrium ensembles of an insulin molecule under amyloidogenic conditions of low pH and high temperature. A bin-based clustering method that uses statistics accumulated in bias exchange metadynamics trajectories was employed to construct a detailed thermodynamic and kinetic model of insulin folding. The highest lifetime, lowest free-energy ensemble identified consisted of native conformations adopted by a folded insulin monomer in solution, namely, the R-, the R^f-, and the T-states of insulin. The lowest free-energy struc

SUBMITTER: Singh R 

PROVIDER: S-EPMC5406382 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature