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 Å 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. © 2007 Elsevier Ltd. All rights reserved.
Yang, J. S., Chen, W. W., Skolnick, J., & Shakhnovich, E. I. (2007). All-Atom Ab Initio Folding of a Diverse Set of Proteins. Structure, 15(1), 53–63. https://doi.org/10.1016/j.str.2006.11.010