In-silico folding of a three helix protein and characterization of its free-energy landscape in an all-atom forcefield

摘要

We report the reproducible first-principles folding of the 40 amino acid, three-helix headpiece of the HIV accessory protein in a recently developed all-atom free-energy forcefield. Six of twenty simulations using an adapted basin-hopping method converged to better than 3 \AA backbone RMS deviation to the experimental structure. Using over 60,000 low-energy conformations of this protein, we constructed a decoy tree that completely characterizes its folding funnel.