Unit

UNIT 28.2 Overview of Protein Folding Mechanisms: Experimental and Theoretical Approaches to Probing Energy Landscapes

  1. Elizabeth R. Morris,
  2. Mark S. Searle

Published Online: 1 APR 2012

DOI: 10.1002/0471140864.ps2802s68

Current Protocols in Protein Science

Current Protocols in Protein Science

How to Cite

Morris, E. R. and Searle, M. S. 2012. Overview of Protein Folding Mechanisms: Experimental and Theoretical Approaches to Probing Energy Landscapes. Current Protocols in Protein Science. 68:28.2:28.2.1–28.2.22.

Author Information

  1. Centre for Biomolecular Sciences, School of Chemistry, University of Nottingham, Nottingham, United Kingdom

Publication History

  1. Published Online: 1 APR 2012
  2. Published Print: APR 2012

Abstract

We present an overview of the current experimental and theoretical approaches to studying protein folding mechanisms, set against current models of the folding energy landscape. We describe how stability and folding kinetics can be determined experimentally and how this data can be interpreted in terms of the characteristic features of various models from the simplest two-state pathway to a multi-state mechanism. We summarize the pros and cons of a range of spectroscopic methods for measuring folding rates and present a theoretical framework, coupled with protein engineering approaches, for elucidating folding mechanisms and structural features of folding transition states. A series of case studies are used to show how experimental kinetic data can be interpreted in the context of non-native interactions, populated intermediates, parallel folding pathways, and sequential transition states. We also show how computational methods now allow transient species of high energy, such as folding transition states, to be modeled on the basis of experimental ϕ-value analysis derived from the effects of point mutations on folding kinetics. Curr. Protoc. Protein Sci. 68:28.2.1-28.2.22. © 2012 by John Wiley & Sons, Inc.

Keywords:

  • protein folding;
  • folding kinetics;
  • energy landscape;
  • protein engineering;
  • folding transition states;
  • molecular dynamics