High-resolution protein folding with a transferable potential

Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18914-9. doi: 10.1073/pnas.0502181102. Epub 2005 Dec 19.

Abstract

A generalized computational method for folding proteins with a fully transferable potential and geometrically realistic all-atom model is presented and tested on seven helix bundle proteins. The protocol, which includes graph-theoretical analysis of the ensemble of resulting folded conformations, was systematically applied and consistently produced structure predictions of approximately 3 A without any knowledge of the native state. To measure and understand the significance of the results, extensive control simulations were conducted. Graph theoretic analysis provides a means for systematically identifying the native fold and provides physical insight, conceptually linking the results to modern theoretical views of protein folding. In addition to presenting a method for prediction of structure and folding mechanism, our model suggests that an accurate all-atom amino acid representation coupled with a physically reasonable atomic interaction potential and hydrogen bonding are essential features for a realistic protein model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computational Biology
  • Computer Simulation
  • Databases, Protein
  • Escherichia coli / metabolism
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Monte Carlo Method
  • Protein Conformation
  • Protein Folding*
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Software
  • Staphylococcus aureus / metabolism
  • Streptococcus / metabolism

Substances

  • Proteins