Protein folding by zipping and assembly

Sefika Ozkan, G. Albert Wu, John D. Chodera, Ken A. Dill

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

How do proteins fold so quickly? Some denatured proteins fold to their native structures in only microseconds, on average, implying that there is a folding "mechanism," i.e., a particular set of events by which the protein short-circuits a broader conformational search. Predicting protein structures using atomically detailed physical models is currently challenging. The most definitive proof of a putative folding mechanism would be whether it speeds up protein structure prediction in physical models. In the zipping and assembly (ZA) mechanism, local structuring happens first at independent sites along the chain, then those structures either grow (zip) or coalescence (assemble) with other structures. Here, we apply the ZA search mechanism to protein native structure prediction by using the AMBER96 force field with a generalized Born/surface area implicit solvent model and sampling by replica exchange molecular dynamics. Starting from open denatured conformations, our algorithm, called the ZA method, converges to an average of 2.2 Å from the Protein Data Bank native structures of eight of nine proteins that we tested, which ranged from 25 to 73 aa in length. In addition, experimental Φ values, where available on these proteins, are consistent with the predicted routes. We conclude that ZA is a viable model for how proteins physically fold. The present work also shows that physics-based force fields are quite good and that physics-based protein structure prediction may be practical, at least for some small proteins.

Original languageEnglish (US)
Pages (from-to)11987-11992
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number29
DOIs
StatePublished - Jul 17 2007

Keywords

  • Protein structure prediction
  • Replica-exchange molecular dynamics

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Protein folding by zipping and assembly'. Together they form a unique fingerprint.

  • Cite this