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Atomic-level observation of macromolecular crowding effects: escape of a protein from the GroEL cage
Journal article   Open access   Peer reviewed

Atomic-level observation of macromolecular crowding effects: escape of a protein from the GroEL cage

Adrian H Elcock
Proceedings of the National Academy of Sciences - PNAS, Vol.100(5), pp.2340-2344
03/04/2003
DOI: 10.1073/pnas.0535055100
PMCID: PMC151342
PMID: 12601146
url
https://doi.org/10.1073/pnas.0535055100View
Published (Version of record) Open Access

Abstract

Experimental work has demonstrated that the efficient operation of the GroEL-GroES chaperonin machinery is sensitive to the presence of macromolecular crowding agents. Here, I describe atomically detailed computer simulations that provide a microscopic view of how crowding effects are exerted. Simulations were performed to compute the free energy required to extract the protein rhodanese from the central cavity of GroEL into solutions containing a range of crowder concentrations. The computed energetics allow the total yield of folded protein to be predicted; the calculated yields show a nonlinear dependence on the concentration of crowding agent identical to that observed experimentally. The close correspondence between simulation and experiment prompts the use of the former in a truly predictive setting: simulations are used to suggest that more effective crowding agents might be designed by exploiting an "agoraphobic effect."
Hydrolysis Thermodynamics Algorithms Biophysical Phenomena Adenosine Triphosphate - metabolism Chaperonin 10 - metabolism Protein Binding Chaperonin 60 - metabolism Biophysics

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