Structure-Based Prediction of Protein-Folding Transition Paths

William M. Jacobs, Eugene I. Shakhnovich

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

We propose a general theory to describe the distribution of protein-folding transition paths. We show that transition paths follow a predictable sequence of high-free-energy transient states that are separated by free-energy barriers. Each transient state corresponds to the assembly of one or more discrete, cooperative units, which are determined directly from the native structure. We show that the transition state on a folding pathway is reached when a small number of critical contacts are formed between a specific set of substructures, after which folding proceeds downhill in free energy. This approach suggests a natural resolution for distinguishing parallel folding pathways and provides a simple means to predict the rate-limiting step in a folding reaction. Our theory identifies a common folding mechanism for proteins with diverse native structures and establishes general principles for the self-assembly of polymers with specific interactions.

Original languageEnglish (US)
Pages (from-to)925-936
Number of pages12
JournalBiophysical Journal
Volume111
Issue number5
DOIs
StatePublished - Sep 6 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics

Fingerprint Dive into the research topics of 'Structure-Based Prediction of Protein-Folding Transition Paths'. Together they form a unique fingerprint.

Cite this