How difficult is it to fold a knotted protein? In silico insights from surface-tethered folding experiments.

ABSTRACT: We explore the effect of surface tethering on the folding process of a lattice protein that contains a trefoil knot in its native structure via Monte Carlo simulations. We show that the outcome of the tethering experiment depends critically on which terminus is used to link the protein to a chemically inert plane. In particular, if surface tethering occurs at the bead that is closer to the knotted core the folding rate becomes exceedingly slow and the protein is not able to find the native structure in all the attempted folding trajectories. Such low folding efficiency is also apparent from the analysis of the probability of knot formation, p(knot), as a function of nativeness. Indeed, p(knot) increases abruptly from ∼0 to ∼1 only when the protein has more than 80% of its native contacts f

SUBMITTER: Soler MA 

PROVIDER: S-EPMC3527535 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature