All-atom ab initio folding of a diverse set of proteins.
Natural proteins fold to a unique, thermodynamically dominant state. Modeling of the folding process and prediction of the native fold of proteins are two major unsolved problems in biophysics. Here, we show successful all-atom ab initio folding of a representative diverse set of proteins by using a minimalist transferable-energy model that consists of two-body atom-atom interactions, hydrogen bonding, and a local sequence-energy term that models sequence-specific chain stiffness. Starting from a random coil, the native-like structure was observed during replica exchange Monte Carlo (REMC) simulation for most proteins regardless of their structural classes; the lowest energy structure was close to native-in the range of 2-6 A root-mean-square deviation (rmsd). Our results demonstrate that the successful folding of a protein chain to its native state is governed by only a few crucial energetic terms.
Yang
Jae Shick
JS
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Chen
William W
WW
Skolnick
Jeffrey
J
Shakhnovich
Eugene I
EI
D008958:Models, Molecular; D009010:Monte Carlo Method; D017510:Protein Folding; D017433:Protein Structure, Secondary