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Distinguishing foldable proteins from nonfolders: when and how do they differ?
Tobin R Sosnick1, R Stephen Berry, Andrés Colubri
1Department of Biochemistry and Molecular Biology and the Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois 60637, USA. trsosnic@midway.uchicago.edu
Proteins
|September 5, 2002
Summary
Protein folding involves fast events. While initial conformational changes are similar for proteins and random sequences, unique correlations emerge in proteins, indicating their foldability.
Area of Science:
- Biochemistry
- Computational Biology
- Protein Folding Dynamics
Background:
- Denatured polypeptides refold through complex conformational changes over various timescales.
- Distinguishing early, productive folding events from generic processes in polypeptides is crucial.
Purpose of the Study:
- To differentiate fast, productive protein folding events from generic processes in polypeptides.
- To investigate the early conformational changes during protein refolding.
Main Methods:
- Utilized an ab initio folding algorithm to model protein folding.
- Compared folding pathways of natural proteins with their random-sequence analogues.
Main Results:
- Proteins and random sequences show similar initial reductions in conformational space exploration.
- Natural protein sequences develop unique three-body correlations, involving hydrophobic group desolvation and hydrogen bond protection.
- These correlations lead to a measurable reduction in accessible configuration space, predicting native structure formation.
Conclusions:
- Early polypeptide conformational changes reflect generic responses to solvent conditions.
- Wild-type protein sequences exhibit specific correlations during folding that indicate foldability.
- The study identifies sequence-specific correlations as key indicators of protein folding propensity.