Mimicking the action of GroEL in molecular dynamics simulations: Application to the refinement of protein structures

Fan, Hao and Mark, Alan E. (2006) Mimicking the action of GroEL in molecular dynamics simulations: Application to the refinement of protein structures. Protein Science, 15 3: 441-448. doi:10.1110/ps.051721006


Author Fan, Hao
Mark, Alan E.
Title Mimicking the action of GroEL in molecular dynamics simulations: Application to the refinement of protein structures
Journal name Protein Science   Check publisher's open access policy
ISSN 0961-8368
Publication date 2006-03-01
Sub-type Article (original research)
DOI 10.1110/ps.051721006
Volume 15
Issue 3
Start page 441
End page 448
Total pages 8
Place of publication New York
Publisher Cold Spring Harbor Laboratory
Collection year 2006
Language eng
Subject C1
250699 Theoretical and Computational Chemistry not elsewhere classified
780103 Chemical sciences
Abstract Bacterial chaperonin, GroEL, together with its co-chaperonin, GroES, facilitates the folding of a variety of polypeptides. Experiments suggest that GroEL stimulates protein folding by multiple cycles of binding and release. Misfolded proteins first bind to an exposed hydrophobic surface on GroEL. GroES then encapsulates the substrate and triggers its release into the central cavity of the GroEL/ES complex for folding. In this work, we investigate the possibility to facilitate protein folding in molecular dynamics simulations by mimicking the effects of GroEL/ES namely, repeated binding and release, together with spatial confinement. During the binding stage, the (metastable) partially folded proteins are allowed to attach spontaneously to a hydrophobic surface within the simulation box. This destabilizes the structures, which are then transferred into a spatially confined cavity for folding. The approach has been tested by attempting to refine protein structural models generated using the ROSETTA procedure for ab initio structure prediction. Dramatic improvements in regard to the deviation of protein models from the corresponding experimental structures were observed. The results suggest that the primary effects of the GroEL/ES system can be mimicked in a simple coarse-grained manner and be used to facilitate protein folding in molecular dynamics simulations. Furthermore, the results Sur port the assumption that the spatial confinement in GroEL/ES assists the folding of encapsulated proteins.
Keyword Protein Structure Prediction
Molecular Dynamics
Structure Refinement
Chaperone
Groel
Biochemistry & Molecular Biology
Crystal-structure
Chaperonin Groel
In-vivo
Binding
Polypeptide
Cavity
Enhancement
Confinement
Resolution
Mechanism
Q-Index Code C1
Additional Notes DOI: 10.1110/ps.051721006

 
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Created: Wed, 15 Aug 2007, 18:55:53 EST