Journal article
Flexibility of the Bacterial Chaperone Trigger Factor in Microsecond-Timescale Molecular Dynamics Simulations
Biophysical journal, Vol.105(3), pp.732-744
08/06/2013
DOI: 10.1016/j.bpj.2013.06.028
PMCID: PMC3736688
PMID: 23931321
Abstract
The bacterial chaperone trigger factor (TF) is the first chaperone to be encountered by a nascent protein chain as it emerges from the ribosome exit tunnel. Experimental results suggest that TF possesses considerable conformational flexibility, and in an attempt to provide an atomic-level view of this flexibility, we have performed independent 1.5-
μ
s molecular dynamics simulations of TF in explicit solvent using two different simulation force fields (OPLS-AA/L and AMBER ff99SB-ILDN). Both simulations indicate that TF possesses tremendous flexibility, with huge excursions from the crystallographic conformation caused by reorientations of the protein’s constituent domains; both simulations also predict the formation of extensive contacts between TF’s PPIase domain and the Arm 1 domain that is involved in nascent-chain binding. In the OPLS simulation, however, TF rapidly settles into a very compact conformation that persists for at least 1
μ
s, whereas in the AMBER simulation, it remains highly dynamic; additional simulations in which the two force fields were swapped suggest that these differences are at least partly attributable to sampling issues. The simulation results provide potential rationalizations of a number of experimental observations regarding TF’s conformational behavior and have implications for using simulations to model TF’s function on translating ribosomes.
Details
- Title: Subtitle
- Flexibility of the Bacterial Chaperone Trigger Factor in Microsecond-Timescale Molecular Dynamics Simulations
- Creators
- Andrew S Thomas - Department of Biochemistry, University of Iowa, Iowa City, IowaSuifang Mao - Department of Biochemistry, University of Iowa, Iowa City, IowaAdrian H Elcock - Department of Biochemistry, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Biophysical journal, Vol.105(3), pp.732-744
- Publisher
- The Biophysical Society
- DOI
- 10.1016/j.bpj.2013.06.028
- PMID
- 23931321
- PMCID
- PMC3736688
- ISSN
- 0006-3495
- eISSN
- 1542-0086
- Language
- English
- Date published
- 08/06/2013
- Academic Unit
- Physics and Astronomy; Biochemistry and Molecular Biology
- Record Identifier
- 9984024420402771
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